G-protein coupled receptors

ABSTRACT

The invention provides human G-protein coupled receptors (GCREC) and polynucleotides which identify and encode GCREC. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of GCREC.

TECHNICAL FIELD

[0001] This invention relates to nucleic acid and amino acid sequencesof G-protein coupled receptors and to the use of these sequences in thediagnosis, treatment, and prevention of cell proliferative,neurological, cardiovascular, gastrointestinal, autoimmune/inflammatory,and metabolic disorders, and viral infections, and in the assessment ofthe effects of exogenous compounds on the expression of nucleic acid andamino acid sequences of G-protein coupled receptors and odorantreceptors. The present invention further relates to the use of specificG-protein coupled receptors to identify molecules that are involved inmodulating taste or olfactory sensation.

BACKGROUND OF THE INVENTION

[0002] Signal transduction is the general process by which cells respondto extracellular signals. Signal transduction across the plasma membranebegins with the binding of a signal molecule, e.g., a hormone,neurotransmitter, or growth factor, to a cell membrane receptor. Thereceptor, thus activated, triggers an intracellular biochemical cascadethat ends with the activation of an intracellular target molecule, suchas a transcription factor. This process of signal transduction regulatesall types of cell functions including cell proliferation,differentiation, and gene transcription. The G-protein coupled receptors(GPCRs), encoded by one of the largest families of genes yet identified,play a central role in the transduction of extracellular signals acrossthe plasma membrane. GPCRs have a proven history of being successfultherapeutic targets.

[0003] GPCRs are integral membrane proteins characterized by thepresence of seven hydrophobic transmembrane domains which together forma bundle of antiparallel alpha (α) helices. GPCRs range in size fromunder 400 to over 1000 amino acids (Strosberg, A. D. (1991) Eur. J.Biochem. 196:1-10; Coughlin, S. R. (1994) Curr. Opin. Cell Biol.6:191-197). The amino-terminus of a GPCR is extracellular, is ofvariable length, and is often glycosylated. The carboxy-terminus iscytoplasmic and generally phosphorylated. Extracellular loops alternatewith intracellular loops and link the transmembrane domains. Cysteinedisulfide bridges linking the second and third extracellular loops mayinteract with agonists and antagonists. The most conserved domains ofGPCRs are the transmembrane domains and the first two cytoplasmic loops.The transmembrane domains account, in part, for structural andfunctional features of the receptor. In most cases, the bundle of αhelices forms a ligand-binding pocket. The extracellular N-terminalsegment, or one or more of the three extracellular loops, may alsoparticipate in ligand binding. Ligand binding activates the receptor byinducing a conformational change in intracellular portions of thereceptor. In turn, the large, third intracellular loop of the activatedreceptor interacts with a heterotrimeric guanine nucleotide binding (G)protein complex which mediates further intracellular signalingactivities, including the activation of second messengers such as cyclicAMP (cAMP), phospholipase C, and inositol triphosphate, and theinteraction of the activated GPCR with ion channel proteins. (See, e.g.,Watson, S. and S. Arkinstall (1994) The G-protein Linked Receptor FactsBook, Academic Press, San Diego Calif., pp. 2-6; Bolander, F. F. (1994)Molecular Endocrinology, Academic Press, San Diego Calif., pp. 162-176;Baldwin, J. M. (1994) Curr. Opin. Cell Biol. 6:180-190.)

[0004] GPCRs include receptors for sensory signal mediators (e.g., lightand olfactory stimulatory molecules); adenosine, γ-aminobutyric acid(GABA), hepatocyte growth factor, melanocortins, neuropeptide Y, opioidpeptides, opsins, somatostatin, tachykinins, vasoactive intestinalpolypeptide family, and vasopressin; biogenic amines (e.g., dopamine,epinephrine and norepinephrine, histamine, glutamate (metabotropiceffect), acetylcholine (muscarinic effect), and serotonin); chemokines;lipid mediators of inflammation (e.g., prostaglandins and prostanoids,platelet activating factor, and leukotrienes); and peptide hormones(e.g., bombesin, bradykinin, calcitonin, C5a anaphylatoxin, endothelin,follicle-stimulating hormone (FSH), gonadotropic-releasing hormone(GnRH), neurokinin, thyrotropin-releasing hormone (TRH), and oxytocin).GPCRs which act as receptors for stimuli that have yet to be identifiedare known as orphan receptors.

[0005] The diversity of the GPCR family is further increased byalternative splicing. Many GPCR genes contain introns, and there arecurrently over 30 such receptors for which splice variants have beenidentified. The largest number of variations are at the proteinC-terminus. N-terminal and cytoplasmic loop variants are also frequent,while variants in the extracellular loops or transmembrane domains areless common. Some receptors have more than one site at which variancecan occur. The splice variants appear to be functionally distinct, basedupon observed differences in distribution, signaling, coupling,regulation, and ligand binding profiles (Kilpatrick, G. J. et al. (1999)Trends Pharmacol. Sci. 20:294-301).

[0006] GPCRs can be divided into three major subfamilies: therhodopsin-like, secretin-like, and metabotropic glutamate receptorsubfamilies. Members of these GPCR subfamilies share similar functionsand the characteristic seven transmembrane structure, but have divergentamino acid sequences. The largest family consists of the rhodopsin-likeGPCRs, which transmit diverse extracellular signals including hormones,neurotransmitters, and light. Rhodopsin is a photosensitive GPCR foundin animal retinas. In vertebrates, rhodopsin molecules are embedded inmembranous stacks found in photoreceptor (rod) cells. Each rhodopsinmolecule responds to a photon of light by triggering a decrease in cGMPlevels which leads to the closure of plasma membrane sodium channels. Inthis manner, a visual signal is converted to a neural impulse. Otherrhodopsin-like GPCRs are directly involved in responding toneurotransmitters. These GPCRs include the receptors for adrenaline(adrenergic receptors), acetylcholine (muscarinic receptors), adenosine,galanin, and glutamate (N-methyl-D-aspartate/NMDA receptors). (Reviewedin Watson, S. and S. Arkinstall (1994) The G-Protein Linked ReceptorFacts Book, Academic Press, San Diego Calif., pp. 7-9, 19-22, 32-35,130-131, 214-216, 221-222; Habert-Ortoli, E. et al. (1994) Proc. Natl.Acad. Sci. USA 91:9780-9783.)

[0007] The galanin receptors mediate the activity of the neuroendocrinepeptide galanin, which inhibits secretion of insulin, acetylcholine,serotonin and noradrenaline, and stimulates prolactin and growth hormonerelease. Galanin receptors are involved in feeding disorders, pain,depression, and Alzheimer's disease (Kask, K. et al. (1997) Life Sci.60:1523-1533). Other nervous system rhodopsin-like GPCRs include agrowing family of receptors for lysophosphatidic acid and otherlysophospholipids, which appear to have roles in development andneuropathology (Chun, J. et al. (1999) Cell Biochem. Biophys.30:213-242).

[0008] The largest subfamily of GPCRs, the olfactory receptors, are alsomembers of the rhodopsin-like GPCR family. These receptors function bytransducing odorant signals. Numerous distinct olfactory receptors arerequired to distinguish different odors. Each olfactory sensory neuronexpresses only one type of olfactory receptor, and distinct spatialzones of neurons expressing distinct receptors are found in nasalpassages. For example, the RA1c receptor, which was isolated from a ratbrain library, has been shown to be limited in expression to verydistinct regions of the brain and a defined zone of the olfactoryepithelium (Raming, K. et al. (1998) Receptors Channels 6:141-151).However, the expression of olfactory-like receptors is not confined toolfactory tissues. For example, three rat genes encoding olfactory-likereceptors having typical GPCR characteristics showed expression patternsnot only in taste and olfactory tissue, but also in male reproductivetissue (Thomas, M. B. et al. (1996) Gene 178:1-5).

[0009] Members of the secretin-like GPCR subfamily have as their ligandspeptide hormones such as secretin, calcitonin, glucagon, growthhormone-releasing hormone, parathyroid hormone, and vasoactiveintestinal peptide. For example, the secretin receptor responds tosecretin, a peptide hormone that stimulates the secretion of enzymes andions in the pancreas and small intestine (Watson, supra, pp. 278-283).Secretin receptors are about 450 amino acids in length and are found inthe plasma membrane of gastrointestinal cells. Binding of secretin toits receptor stimulates the production of cAMP.

[0010] Examples of secretin-like GPCRs implicated in inflammation andthe immune response include the EGF module-containing, mucin-likehormone receptor (Emr1) and CD97 receptor proteins. These GPCRs aremembers of the recently characterized EGF-TM7 receptors subfamily. Theseseven transmembrane hormone receptors exist as heterodimers in vivo andcontain between three and seven potential calcium-binding EGF-likemotifs. CD97 is predominantly expressed in leukocytes and is markedlyupregulated on activated B and T cells (McKnight, A. J. and S. Gordon(1998) J. Leukoc. Biol. 63:271-280). Another subfamily of thesecretin-like GPCRs was recently defined by the Ig. Hepta protein.Ig-Hepta contains a seven transmembrane domain characteristic ofsecretin-like GPCRs, as well as a large extracellular domain containingtwo immunoglobulin-like repeats. Ig-Hepta expression is localized to theaveolar walls of the lung and the intercalated cells in the collectingduct of the kidney, suggesting a role for Ig-Hepta in pH sensing orregulation (Abe, J. et al. (1999) J. Biol. Chem. 274:19957-19964).

[0011] The third GPCR subfamily is the metabotropic glutamate receptorfamily. Glutamate is the major excitatory neurotransmitter in thecentral nervous system. The metabotropic glutamate receptors modulatethe activity of intracellular effectors, and are involved in long-termpotentiation (Watson, supra, p.130). The Ca²⁺-sensing receptor, whichsenses changes in the extracellular concentration of calcium ions, has alarge extracellular domain including clusters of acidic amino acidswhich may be involved in calcium binding. The metabotropic glutamatereceptor family also includes pheromone receptors, the GABA_(B)receptors, and the taste receptors.

[0012] Other subfamilies of GPCRs include two groups of chemoreceptorgenes found in the nematodes Caenorhabditis elegans and Caenorhabditisbriggsae, which are distantly related to the mammalian olfactoryreceptor genes. The yeast pheromone receptors STE2 and STE3, involved inthe response to mating factors on the cell membrane, have their ownseven-transmembrane signature, as do the cAMP receptors from the slimemold Dictyostelium discoideum, which are thought to regulate theaggregation of individual cells and control the expression of numerousdevelopmentally-regulated genes.

[0013] GPCR mutations, which may cause loss of function or constitutiveactivation, have been associated with numerous human diseases (Coughlin,supra). For instance, retinitis pigmentosa may arise from mutations inthe rhodopsin gene. Furthermore, somatic activating mutations in thethyrotropin receptor have been reported to cause hyperfunctioningthyroid adenomas, suggesting that certain GPCRs susceptible toconstitutive activation may behave as protooncogenes (Parma, J. et al.(1993) Nature 365:649-651). GPCR receptors for the following ligandsalso contain mutations associated with human disease: luteinizinghormone (precocious puberty); vasopressin V₂ (X-linked nephrogenicdiabetes); glucagon (diabetes and hypertension); calcium(hyperparathyroidism, hypocalcuria, hypercalcemia); parathyroid hormone(short limbed dwarfism); β₃-adrenoceptor (obesity, non-insulin-dependentdiabetes mellitus); growth hormone releasing hormone (dwarfism); andadrenocorticotropin (glucocorticoid deficiency) (Wilson, S. et al.(1998) Br. J. Pharmocol. 125:1387-1392; Stadel, J. M. et al. (1997)Trends Pharmacol. Sci. 18:430-437). GPCRs are also involved indepression, schizophrenia, sleeplessness, hypertension, anxiety, stress,renal failure, and several cardiovascular disorders (Horn, F. and G.Vriend (1998) J. Mol. Med. 76:464-468).

[0014] In addition, within the past 20 years several hundred new drugshave been recognized that are directed towards activating or inhibitingGPCRs. The therapeutic targets of these drugs span a wide range ofdiseases and disorders, including cardiovascular, gastrointestinal, andcentral nervous system disorders as well as cancer, osteoporosis andendometriosis (Wilson, supra; Stadel, supra). For example, the dopamineagonist L-dopa is used to treat Parkinson's disease, while a dopamineantagonist is used to treat schizophrenia and the early stages ofHuntington's disease. Agonists and antagonists of adrenoceptors havebeen used for the treatment of asthma, high blood pressure, othercardiovascular disorders, and anxiety; muscarinic agonists are used inthe treatment of glaucoma and tachycardia; serotonin 5HT1D antagonistsare used against migraine; and histamine H1 antagonists are used againstallergic and anaphylactic reactions, hay fever, itching, and motionsickness (Horn, supra).

[0015] Recent research suggests potential future therapeutic uses forGPCRs in the treatment of metabolic disorders including diabetes,obesity, and osteoporosis. For example, mutant V2 vasopressin receptorscausing nephrogenic diabetes could be functionally rescued in vitro byco-expression of a C-terminal V2 receptor peptide spanning the regioncontaining the mutations. This result suggests a possible novel strategyfor disease treatment (Schöneberg, T. et al. (1996) EMBO J.15:1283-1291). Mutations in melanocortin-4 receptor (MC4R) areimplicated in human weight regulation and obesity. As with thevasopressin V2 receptor mutants, these MC4R mutants are defective intrafficking to the plasma membrane (Ho, G. and R. G. MacKenzie (1999) J.Biol. Chem. 274:35816-35822), and thus might be treated with a similarstrategy. The type 1 receptor for parathyroid hormone (PTH) is a GPCRthat mediates the PTH-dependent regulation of calcium homeostasis in thebloodstream. Study of PTH/receptor interactions may enable thedevelopment of novel PTH receptor ligands for the treatment ofosteoporosis (Mannstadt, M. et al. (1999) Am. J. Physiol.277:F665-F675).

[0016] The chemokine receptor group of GPCRs have potential therapeuticutility in inflammation and infectious disease. (For review, see Locati,M. and P. M. Murphy (1999) Annu. Rev. Med. 50:425-440.) Chemokines aresmall polypeptides that act as intracellular signals in the regulationof leukocyte trafficking, hematopoiesis, and angiogenesis. Targeteddisruption of various chemokine receptors in mice indicates that thesereceptors play roles in pathologic inflammation and in autoimmunedisorders such as multiple sclerosis. Chemokine receptors are alsoexploited by infectious agents, including herpesviruses and the humanimmunodeficiency virus (HIV-1) to facilitate infection. A truncatedversion of chemokine receptor CCR5, which acts as a coreceptor forinfection of T-cells by HIV-1, results in resistance to AIDS, suggestingthat CCR5 antagonists could be useful in preventing the development ofAIDS.

[0017] The involvement of some GPCRs in taste and olfactory sensationhas been reported. Complete or partial sequences of numerous human andother eukaryotic sensory receptors are currently known. (See, e.g.,Pilpel, Y. and D. Lancet (1999) Protein Sci. 8:969-977; Mombaerts, P.(1999) Annu. Rev. Neurosci. 22:487-509. See also, e.g., patents EP867508A2; U.S. Pat. No. 5,874,243; WO 92/17585; WO 95/18140; WO97/17444; and WO 99/67282.) It has been reported that the human genomecontains approximately one thousand genes that encode a diverserepertoire of olfactory receptors (Rouquier, S. et al. (1998) Nat.Genet. 18:243-250; Trask, B. J. et al. (1998) Hum. Mol. Genet.7:2007-2020).

[0018] IL-5 Treatment and Immune Response

[0019] Cells undergoing neoplastic growth gradually progress to invasivecarcinoma and become metastatic. Factors involved in tumor progressionand malignant transformation include genetic factors, environmentalfactors, growth factors, and hormones. Histological and molecularevaluation of breast tumors has revealed that the development of breastcancer evolves through a multi-step process whereby pre-malignantmammary epithelial cells undergo a relatively defined sequence of eventsleading to tumor formation.

[0020] Neoplastic growth is mediated by a variety of factors such asInterleukin 5 (IL-5), a T cell-derived factor that promotes theproliferation, differentiation, and activation of eosinophils. IL-5 hasalso been known as T cell replacing factor (TRF), B cell growth factorII (BCGFII), B cell differentiation factor m (BCDF m), eosinophildifferentiation factor (EDF), and eosinophil colony-stimulating factor(Eo-CSF). IL-5 exerts its activity on target cells by binding tospecific cell surface receptors. The effect of IL-5 may be observed inhuman peripheral blood mononuclear cells (PBMCs), which contain about52% lymphocytes (12% B lymphocytes, 40% T lymphocytes {25% CD4+ and 15%CD8+}), 20% NK cells, 25% monocytes, and 3% various cells that includedendritic cells and progenitor cells.

[0021] The discovery of new G-protein coupled receptors and thepolynucleotides encoding them satisfies a need in the art by providingnew compositions which are useful in the diagnosis, prevention, andtreatment of cell proliferative, neurological, cardiovascular,gastrointestinal, autoimrnune/inflammatory, and metabolic disorders, andviral infections, and in the assessment of the effects of exogenouscompounds on the expression of nucleic acid and amino acid sequences ofG-protein coupled receptors.

SUMMARY OF THE INVENTION

[0022] The invention features purified polypeptides, G-protein coupledreceptors, referred to collectively as “GCREC” and individually as“GCREC-1,” “GCREC-2,” “GCREC-3,” “GCREC4,” “GCREC-5,” “GCREC-6,”“GCREC-7,” “GCREC-8,” “GCREC-9,” “GCREC-10,” “GCREC-11,” “GCREC-12,”“GCREC-13,” “GCREC-14,” “GCREC-15,” “GCREC-16,” “GCREC-17,” “GCREC-18,”“GCREC-19,” “GCREC-20,” “GCREC-21,” “GCREC-22,” “GCREC-23,” “GCREC-24,”“GCREC-25,” “GCREC-26,” “GCREC-27,” “GCREC-28,” “GCREC-29,” “GCREC-30,”“GCREC-31,” “GCREC-32,” “GCREC-33,” “GCREC-34,” “GCREC-35,” “GCREC-36,”“GCREC-37,” “GCREC-38,” “GCREC-39,” “GCREC-40,” “GCREC-41,” “GCREC-42,”“GCREC-43,” “GCREC-44,” “GCREC-45,” “GCREC-46,” “GCREC-47,” and“GCREC-48.” In one aspect, the invention provides an isolatedpolypeptide selected from the group consisting of a) a polypeptidecomprising an amino acid sequence selected from the group consisting ofSEQ ID NO:1-48, b) a polypeptide comprising a naturally occurring aminoacid sequence at least 90% identical to an amino acid sequence selectedfrom the group consisting of SEQ ID NO:1-48, c) a biologically activefragment of a polypeptide having an amino acid sequence selected fromthe group consisting of SEQ ID NO:1-48, and d) an immunogenic fragmentof a polypeptide having an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48. In one alternative, the invention providesan isolated polypeptide comprising the amino acid sequence of SEQ IDNO:1-48.

[0023] The invention further provides an isolated polynucleotideencoding a polypeptide selected from the group consisting of a) apolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48, b) a polypeptide comprising a naturallyoccurring amino acid sequence at least 90% identical to an amino acidsequence selected from the group consisting of SEQ ID NO:1-48, c) abiologically active fragment of a polypeptide having an amino acidsequence selected from the group consisting of SEQ ID NO:1-48, and d) animmunogenic fragment of a polypeptide having an amino acid sequenceselected from the group consisting of SEQ ID NO:1-48. In onealternative, the polynucleotide encodes a polypeptide selected from thegroup consisting of SEQ ID NO:1-48. In another alternative, thepolynucleotide is selected from the group consisting of SEQ ID NO:49-96.

[0024] The invention additionally provides G-protein coupled receptorsthat are involved in olfactory and/or taste sensation. The inventionfurther provides polynucleotide sequences that encode said G-proteincoupled receptors.

[0025] Additionally, the invention provides a recombinant polynucleotidecomprising a promoter sequence operably linked to a polynucleotideencoding a polypeptide selected from the group consisting of a) apolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48, b) a polypeptide comprising a naturallyoccurring amino acid sequence at least 90% identical to an amino acidsequence selected from the group consisting of SEQ ID NO:1-48, c) abiologically active fragment of a polypeptide having an amino acidsequence selected from the group consisting of SEQ ID NO:1-48, and d) animmunogenic fragment of a polypeptide having an amino acid sequenceselected from the group consisting of SEQ ID NO:1-48. In onealternative, the invention provides a cell transformed with therecombinant polynucleotide. In another alternative, the inventionprovides a transgenic organism comprising the recombinantpolynucleotide.

[0026] The invention also provides a method for producing a polypeptideselected from the group consisting of a) a polypeptide comprising anamino acid sequence selected from the group consisting of SEQ IDNO:1-48, b) a polypeptide comprising a naturally occurring amino acidsequence at least 90% identical to an amino acid sequence selected fromthe group consisting of SEQ ID NO:1-48, c) a biologically activefragment of a polypeptide having an amino acid sequence selected fromthe group consisting of SEQ ID NO:1-48, and d) an immunogenic fragmentof a polypeptide having an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48. The method comprises a) culturing a cellunder conditions suitable for expression of the polypeptide, whereinsaid cell is transformed with a recombinant polynucleotide comprising apromoter sequence operably linked to a polynucleotide encoding thepolypeptide, and b) recovering the polypeptide so expressed.

[0027] Additionally, the invention provides an isolated antibody whichspecifically binds to a polypeptide selected from the group consistingof a) a polypeptide comprising an amino acid sequence selected from thegroup consisting of SEQ ID NO:1-48, b) a polypeptide comprising anaturally occurring amino acid sequence at least 90% identical to anamino acid sequence selected from the group consisting of SEQ IDNO:1-48, c) a biologically active fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-48, and d) an immunogenic fragment of a polypeptide having an aminoacid sequence selected from the group consisting of SEQ ID NO:1-48.

[0028] The invention further provides an isolated polynucleotideselected from the group consisting of a) a polynucleotide comprising apolynucleotide sequence selected from the group consisting of SEQ IDNO:49-96, b) a polynucleotide comprising a naturally occurringpolynucleotide sequence at least 90% identical to a polynucleotidesequence selected from the group consisting of SEQ ID NO:49-96, c) apolynucleotide complementary to the polynucleotide of a), d) apolynucleotide complementary to the polynucleotide of b), and e) an RNAequivalent of a)-d). In one alternative, the polynucleotide comprises atleast 60 contiguous nucleotides.

[0029] Additionally, the invention provides a method for detecting atarget polynucleotide in a sample, said target polynucleotide having asequence of a polynucleotide selected from the group consisting of a) apolynucleotide comprising a polynucleotide sequence selected from thegroup consisting of SEQ ID NO:49-96, b) a polynucleotide comprising anaturally occurring polynucleotide sequence at least 90% identical to apolynucleotide sequence selected from the group consisting of SEQ IDNO:49-96, c) a polynucleotide complementary to the polynucleotide of a),d) a polynucleotide complementary to the polynucleotide of b), and e) anRNA equivalent of a)-d). The method comprises a) hybridizing the samplewith a probe comprising at least 20 contiguous nucleotides comprising asequence complementary to said target polynucleotide in the sample, andwhich probe specifically hybridizes to said target polynucleotide, underconditions whereby a hybridization complex is formed between said probeand said target polynucleotide or fragments thereof, and b) detectingthe presence or absence of said hybridization complex, and optionally,if present, the amount thereof. In one alternative, the probe comprisesat least 60 contiguous nucleotides.

[0030] The invention further provides a method for detecting a targetpolynucleotide in a sample, said target polynucleotide having a sequenceof a polynucleotide selected from the group consisting of a) apolynucleotide comprising a polynucleotide sequence selected from thegroup consisting of SEQ ID NO:49-96, b) a polynucleotide comprising anaturally occurring polynucleotide sequence at least 90% identical to apolynucleotide sequence selected from the group consisting of SEQ IDNO:49-96, c) a polynucleotide complementary to the polynucleotide of a),d) a polynucleotide complementary to the polynucleotide of b), and e) anRNA equivalent of a)-d). The method comprises a) amplifying said targetpolynucleotide or fragment thereof using polymerase chain reactionamplification, and b) detecting the presence or absence of saidamplified target polynucleotide or fragment thereof, and, optionally, ifpresent, the amount thereof.

[0031] The invention further provides a composition comprising aneffective amount of a polypeptide selected from the group consisting ofa) a polypeptide comprising an amino acid sequence selected from thegroup consisting of SEQ ID NO:1-48, b) a polypeptide comprising anaturally occurring amino acid sequence at least 90% identical to anamino acid sequence selected from the group consisting of SEQ IDNO:1-48, c) a biologically active fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-48, and d) an immunogenic fragment of a polypeptide having an aminoacid sequence selected from the group consisting of SEQ ID NO:1-48, anda pharmaceutically acceptable excipient. In one embodiment, thecomposition comprises an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48. The invention additionally provides amethod of treating a disease or condition associated with decreasedexpression of functional GCREC, comprising administering to a patient inneed of such treatment the composition.

[0032] The invention also provides a method for screening a compound foreffectiveness as an agonist of a polypeptide selected from the groupconsisting of a) a polypeptide comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:1-48, b) a polypeptidecomprising a naturally occurring amino acid sequence at least 90%identical to an amino acid sequence selected from the group consistingof SEQ ID NO:1-48, c) a biologically active fragment of a polypeptidehaving an amino acid sequence selected from the group consisting of SEQID NO:1-48, and d) an immunogenic fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-48. The method comprises a) exposing a sample comprising thepolypeptide to a compound, and b) detecting agonist activity in thesample. In one alternative, the invention provides a compositioncomprising an agonist compound identified by the method and apharmaceutically acceptable excipient. In another alternative, theinvention provides a method of treating a disease or conditionassociated with decreased expression of functional GCREC, comprisingadministering to a patient in need of such treatment the composition.

[0033] Additionally, the invention provides a method for screening acompound for effectiveness as an antagonist of a polypeptide selectedfrom the group consisting of a) a polypeptide comprising an amino acidsequence selected from the group consisting of SEQ ID NO:1-48, b) apolypeptide comprising a naturally occurring amino acid sequence atleast 90% identical to an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48, c) a biologically active fragment of apolypeptide having an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48, and d) an immunogenic fragment of apolypeptide having an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48. The method comprises a) exposing a samplecomprising the polypeptide to a compound, and b) detecting antagonistactivity in the sample. In one alternative, the invention provides acomposition comprising an antagonist compound identified by the methodand a pharmaceutically acceptable excipient. In another alternative, theinvention provides a method of treating a disease or conditionassociated with overexpression of functional GCREC, comprisingadministering to a patient in need of such treatment the composition.

[0034] The invention further provides a method of screening for acompound that specifically binds to a polypeptide selected from thegroup consisting of a) a polypeptide comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:1-48, b) a polypeptidecomprising a naturally occurring amino acid sequence at least 90%identical to an amino acid sequence selected from the group consistingof SEQ ID NO:1-48, c) a biologically active fragment of a polypeptidehaving an amino acid sequence selected from the group consisting of SEQID NO:1-48, and d) an immunogenic fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-48. The method comprises a) combining the polypeptide with at leastone test compound under suitable conditions, and b) detecting binding ofthe polypeptide to the test compound, thereby identifying a compoundthat specifically binds to the polypeptide.

[0035] The invention further provides a method of screening for acompound that modulates the activity of a polypeptide selected from thegroup consisting of a) a polypeptide comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:1-48, b) a polypeptidecomprising a naturally occurring amino acid sequence at least 90%identical to an amino acid sequence selected from the group consistingof SEQ ID NO:1-48, c) a biologically active fragment of a polypeptidehaving an amino acid sequence selected from the group consisting of SEQID NO:1-48, and d) an immunogenic fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-48. The method comprises a) combining the polypeptide with at leastone test compound under conditions permissive for the activity of thepolypeptide, b) assessing the activity of the polypeptide in thepresence of the test compound, and c) comparing the activity of thepolypeptide in the presence of the test compound with the activity ofthe polypeptide in the absence of the test compound, wherein a change inthe activity of the polypeptide in the presence of the test compound isindicative of a compound that modulates the activity of the polypeptide.

[0036] The invention further provides methods of using G-protein coupledreceptors of the invention involved in olfactory and/or taste sensation,biologically active fragments thereof (including those having receptoractivity), and amino acid sequences having at least 90% sequenceidentity therewith, to identify compounds that agonize or antagonize theforegoing receptor polypeptides. These compounds are useful formodulating, blocking and/or mimicking specific tastes and/or odors.

[0037] The present invention also relates to the use of olfactory and/ortaste receptors of the invention, biologically active fragments thereof(including those having receptor activity), and polypeptides having atleast 90% sequence identity therewith, in combination with one or moreother olfactory and/or taste receptor polypeptides, to identify acompound or plurality of compounds that modulate, mimic, and/or block aspecific olfactory and/or taste sensation.

[0038] The invention also relates to cells that express an olfactory ortaste receptor polypeptide of the invention, a biologically activefragment thereof (including those having receptor activity), or apolypeptide having at least 90% sequence identity therewith, and the useof such cells in cell-based screens to identify molecules that modulate,mimic, and/or block specific olfactory or taste sensations.

[0039] Still further, the invention relates to a cell that co-expressesat least one olfactory or taste G-protein coupled receptor polypeptideof the invention, and a G-protein, and optionally one or more otherolfactory and/or taste G-protein coupled receptor polypeptides, and theuse of such a cell in screens to identify molecules that modulate,mimic, and/or block specific olfactory and/or taste sensations.

[0040] The invention further provides a method for screening a compoundfor effectiveness in altering expression of a target polynucleotide,wherein said target polynucleotide comprises a polynucleotide sequenceselected from the group consisting of SEQ ID NO:49-96, the methodcomprising a) exposing a sample comprising the target polynucleotide toa compound, b) detecting altered expression of the targetpolynucleotide, and c) comparing the expression of the targetpolynucleotide in the presence of varying amounts of the compound and inthe absence of the compound.

[0041] The invention further provides a method for assessing toxicity ofa test compound, said method comprising a) treating a biological samplecontaining nucleic acids with the test compound; b) hybridizing thenucleic acids of the treated biological sample with a probe comprisingat least 20 contiguous nucleotides of a polynucleotide selected from thegroup consisting of i) a polynucleotide comprising a polynucleotidesequence selected from the group consisting of SEQ ID NO:49-96, ii) apolynucleotide comprising a naturally occurring polynucleotide sequenceat least 90% identical to a polynucleotide sequence selected from thegroup consisting of SEQ ID NO:49-96, iii) a polynucleotide having asequence complementary to i), iv) a polynucleotide complementary to thepolynucleotide of ii), and v) an RNA equivalent of i)-iv). Hybridizationoccurs under conditions whereby a specific hybridization complex isformed between said probe and a target polynucleotide in the biologicalsample, said target polynucleotide selected from the group consisting ofi) a polynucleotide comprising a polynucleotide sequence selected fromthe group consisting of SEQ ID NO:49-96, ii) a polynucleotide comprisinga naturally occurring polynucleotide sequence at least 90% identical toa polynucleotide sequence selected from the group consisting of SEQ IDNO:49-96, iii) a polynucleotide complementary to the polynucleotide ofi), iv) a polynucleotide complementary to the polynucleotide of ii), andv) an RNA equivalent of i)-iv). Alternatively, the target polynucleotidecomprises a fragment of a polynucleotide sequence selected from thegroup consisting of i)-v) above; c) quantifying the amount ofhybridization complex; and d) comparing the amount of hybridizationcomplex in the treated biological sample with the amount ofhybridization complex in an untreated biological sample, wherein adifference in the amount of hybridization complex in the treatedbiological sample is indicative of toxicity of the test compound.

BRIEF DESCRIPTION OF THE TABLES

[0042] Table 1 summarizes the nomenclature for the full lengthpolynucleotide and polypeptide sequences of the present invention.

[0043] Table 2 shows the GenBank identification number and annotation ofthe nearest GenBank homolog for polypeptides of the invention. Theprobability scores for the matches between each polypeptide and itshomolog(s) are also shown.

[0044] Table 3 shows structural features of polypeptide sequences of theinvention, including predicted motifs and domains, along with themethods, algorithms, and searchable databases used for analysis of thepolypeptides.

[0045] Table 4 lists the cDNA and/or genomic DNA fragments which wereused to assemble polynucleotide sequences of the invention, along withselected fragments of the polynucleotide sequences.

[0046] Table 5 shows the representative cDNA library for polynucleotidesof the invention.

[0047] Table 6 provides an appendix which describes the tissues andvectors used for construction of the cDNA libraries shown in Table 5.

[0048] Table 7 shows the tools, programs, and algorithms used to analyzethe polynucleotides and polypeptides of the invention, along withapplicable descriptions, references, and threshold parameters.

DESCRIPTION OF THE INVENTION

[0049] Before the present proteins, nucleotide sequences, and methodsare described, it is understood that this invention is not limited tothe particular machines, materials and methods described, as these mayvary. It is also to be understood that the terminology used herein isfor the purpose of describing particular embodiments only, and is notintended to limit the scope of the present invention which will belimited only by the appended claims.

[0050] It must be noted that as used herein and in the appended claims,the singular forms “a,” “an,” and “the” include plural reference unlessthe context clearly dictates otherwise. Thus, for example, a referenceto “a host cell” includes a plurality of such host cells, and areference to “an antibody” is a reference to one or more antibodies andequivalents thereof known to those skilled in the art, and so forth.

[0051] Unless defined otherwise, all technical and scientific terms usedherein have the same meanings as commonly understood by one of ordinaryskill in the art to which this invention belongs. Although any machines,materials, and methods similar or equivalent to those described hereincan be used to practice or test the present invention, the preferredmachines, materials and methods are now described. All publicationsmentioned herein are cited for the purpose of describing and disclosingthe cell lines, protocols, reagents and vectors which are reported inthe publications and which might be used in connection with theinvention. Nothing herein is to be construed as an admission that theinvention is not entitled to antedate such disclosure by virtue of priorinvention.

[0052] Definitions

[0053] “GCREC” refers to the amino acid sequences of substantiallypurified GCREC obtained from any species, particularly a mammalianspecies, including bovine, ovine, porcine, murine, equine, and human,and from any source, whether natural, synthetic, semi-synthetic, orrecombinant.

[0054] The term “agonist” refers to a molecule which intensifies ormimics the biological activity of GCREC. Agonists may include proteins,nucleic acids, carbohydrates, small molecules, or any other compound orcomposition which modulates the activity of GCREC either by directlyinteracting with GCREC or by acting on components of the biologicalpathway in which GCREC participates.

[0055] An “allelic variant” is an alternative form of the gene encodingGCREC. Allelic variants may result from at least one mutation in thenucleic acid sequence and may result in altered mRNAs or in polypeptideswhose structure or function may or may not be altered. A gene may havenone, one, or many allelic variants of its naturally occurring form.Common mutational changes which give rise to allelic variants aregenerally ascribed to natural deletions, additions, or substitutions ofnucleotides. Each of these types of changes may occur alone, or incombination with the others, one or more times in a given sequence.

[0056] “Altered” nucleic acid sequences encoding GCREC include thosesequences with deletions, insertions, or substitutions of differentnucleotides, resulting in a polypeptide the same as GCREC or apolypeptide with at least one functional characteristic of GCREC.Included within this definition are polymorphisms which may or may notbe readily detectable using a particular oligonucleotide probe of thepolynucleotide encoding GCREC, and improper or unexpected hybridizationto allelic variants, with a locus other than the normal chromosomallocus for the polynucleotide sequence encoding GCREC. The encodedprotein may also be “altered,” and may contain deletions, insertions, orsubstitutions of amino acid residues which produce a silent change andresult in a functionally equivalent GCREC. Deliberate amino acidsubstitutions may be made on the basis of similarity in polarity,charge, solubility, hydrophobicity, hydrophilicity, and/or theamphipathic nature of the residues, as long as the biological orimmunological activity of GCREC is retained. For example, negativelycharged amino acids may include aspartic acid and glutamic acid, andpositively charged amino acids may include lysine and arginine. Aminoacids with uncharged polar side chains having similar hydrophilicityvalues may include: asparagine and glutamine; and serine and threonine.Amino acids with uncharged side chains having similar hydrophilicityvalues may include: leucine, isoleucine, and valine; glycine andalanine; and phenylalanine and tyrosine.

[0057] The terms “amino acid” and “amino acid sequence” refer to anoligopeptide, peptide, polypeptide, or protein sequence, or a fragmentof any of these, and to naturally occurring or synthetic molecules.Where “amino acid sequence” is recited to refer to a sequence of anaturally occurring protein molecule, “amino acid sequence” and liketerms are not meant to limit the amino acid sequence to the completenative amino acid sequence associated with the recited protein molecule.

[0058] “Amplification” relates to the production of additional copies ofa nucleic acid sequence. Amplification is generally carried out usingpolymerase chain reaction (PCR) technologies well known in the art.

[0059] The term “antagonist” refers to a molecule which inhibits orattenuates the biological activity of GCREC. Antagonists may includeproteins such as antibodies, nucleic acids, carbohydrates, smallmolecules, or any other compound or composition which modulates theactivity of GCREC either by directly interacting with GCREC or by actingon components of the biological pathway in which GCREC participates.

[0060] The term “antibody” refers to intact immunoglobulin molecules aswell as to fragments thereof, such as Fab, F(ab′)₂, and Fv fragments,which are capable of binding an epitopic determinant. Antibodies thatbind GCREC polypeptides can be prepared using intact polypeptides orusing fragments containing small peptides of interest as the immunizingantigen. The polypeptide or oligopeptide used to immunize an animal(e.g., a mouse, a rat, or a rabbit) can be derived from the translationof RNA, or synthesized chemically, and can be conjugated to a carrierprotein if desired. Commonly used carriers that are chemically coupledto peptides include bovine serum albumin, thyroglobulin, and keyholelimpet hemocyanin (KLH). The coupled peptide is then used to immunizethe animal.

[0061] The term “antigenic determinant” refers to that region of amolecule (i.e., an epitope) that makes contact with a particularantibody. When a protein or a fragment of a protein is used to immunizea host animal, numerous regions of the protein may induce the productionof antibodies which bind specifically to antigenic determinants(particular regions or three-dimensional structures on the protein). Anantigenic determinant may compete with the intact antigen (i.e., theimmunogen used to elicit the immune response) for binding to anantibody.

[0062] The term “aptamer” refers to a nucleic acid or oligonucleotidemolecule that binds to a specific molecular target. Aptamers are derivedfrom an in vitro evolutionary process (e.g., SELEX (Systematic Evolutionof Ligands by EXponential Enrichment), described in U.S. Pat. No.5,270,163), which selects for target-specific aptamer sequences fromlarge combinatorial libraries. Aptamer compositions may bedouble-stranded or single-stranded, and may includedeoxyribonucleotides, ribonucleotides, nucleotide derivatives, or othernucleotide-like molecules. The nucleotide components of an aptamer mayhave modified sugar groups (e.g., the 2′-OH group of a ribonucleotidemay be replaced by 2′-F or 2′-NH₂), which may improve a desiredproperty, e.g., resistance to nucleases or longer lifetime in blood.Aptamers may be conjugated to other molecules, e.g., a high molecularweight carrier to slow clearance of the aptamer from the circulatorysystem. Aptamers may be specifically cross-linked to their cognateligands, e.g., by photo-activation of a cross-linker. (See, e.g., Brody,E. N. and L. Gold (2000) J. Biotechnol. 74:5-13.)

[0063] The term “intramer” refers to an aptamer which is expressed invivo. For example, a vaccinia virus-based RNA expression system has beenused to express specific RNA aptamers at high levels in the cytoplasm ofleukocytes (Blind, M. et al. (1999) Proc. Natl Acad. Sci. USA96:3606-3610).

[0064] The term “spiegelmer” refers to an aptamer which includes L-DNA,L-RNA, or other left-handed nucleotide derivatives or nucleotide-likemolecules. Aptamers containing left-handed nucleotides are resistant todegradation by naturally occurring enzymes, which normally act onsubstrates containing right-handed nucleotides.

[0065] The term “antisense” refers to any composition capable ofbase-pairing with the “sense” (coding) strand of a specific nucleic acidsequence. Antisense compositions may include DNA; RNA; peptide nucleicacid (PNA); oligonucleotides having modified backbone linkages such asphosphorothioates, methylphosphonates, or benzylphosphonates;oligonucleotides having modified sugar groups such as 2′-methoxyethylsugars or 2′-methoxyethoxy sugars; or oligonucleotides having modifiedbases such as 5-methyl cytosine, 2′-deoxyuracil, or7-deaza-2′-deoxyguanosine. Antisense molecules may be produced by anymethod including chemical synthesis or transcription. Once introducedinto a cell, the complementary antisense molecule base-pairs with anaturally occurring nucleic acid sequence produced by the cell to formduplexes which block either transcription or translation. Thedesignation “negative” or “minus” can refer to the antisense strand, andthe designation “positive” or “plus” can refer to the sense strand of areference DNA molecule.

[0066] The term “biologically active” refers to a protein havingstructural, regulatory, or biochemical functions of a naturallyoccurring molecule. Likewise, “immunologically active” or “immunogenic”refers to the capability of the natural, recombinant, or syntheticGCREC, or of any oligopeptide thereof, to induce a specific immuneresponse in appropriate animals or cells and to bind with specificantibodies.

[0067] “Complementary” describes the relationship between twosingle-stranded nucleic acid sequences that anneal by base-pairing. Forexample, 5′-AGT-3′ pairs with its complement, 3′-TCA-5′.

[0068] A “composition comprising a given polynucleotide sequence” and a“composition comprising a given amino acid sequence” refer broadly toany composition containing the given polynucleotide or amino acidsequence. The composition may comprise a dry formulation or an aqueoussolution. Compositions comprising polynucleotide sequences encodingGCREC or fragments of GCREC may be employed as hybridization probes. Theprobes may be stored in freeze-dried form and may be associated with astabilizing agent such as a carbohydrate. In hybridizations, the probemay be deployed in an aqueous solution containing salts (e.g., NaCl),detergents (e.g., sodium dodecyl sulfate; SDS), and other components(e.g., Denhardt's solution, dry milk, salmon sperm DNA, etc.).

[0069] “Consensus sequence” refers to a nucleic acid sequence which hasbeen subjected to repeated DNA sequence analysis to resolve uncalledbases, extended using the XL-PCR kit (Applied Biosystems, Foster CityCalif.) in the 5′ and/or the 3′ direction, and resequenced, or which hasbeen assembled from one or more overlapping cDNA, EST, or genomic DNAfragments using a computer program for fragment assembly, such as theGELVIEW fragment assembly system (GCG, Madison Wis.) or Phrap(University of Washington, Seattle Wash.). Some sequences have been bothextended and assembled to produce the consensus sequence.

[0070] “Conservative amino acid substitutions” are those substitutionsthat are predicted to least interfere with the properties of theoriginal protein, i.e., the structure and especially the function of theprotein is conserved and not significantly changed by suchsubstitutions. The table below shows amino acids which may besubstituted for an original amino acid in a protein and which areregarded as conservative amino acid substitutions. Original ResidueConservative Substitution Ala Gly, Ser Arg His, Lys Asn Asp, Gln, HisAsp Asn, Glu Cys Ala, Ser Gln Asn, Glu, His Glu Asp, Gln, His Gly AlaHis Asn, Arg, Gln, Glu Ile Leu, Val Leu Ile, Val Lys Arg, Gln, Glu MetLeu, Ile Phe His, Met, Leu, Trp, Tyr Ser Cys, Thr Thr Ser, Val Trp Phe,Tyr Tyr His, Phe, Trp Val Ile, Leu, Thr

[0071] Conservative amino acid substitutions generally maintain (a) thestructure of the polypeptide backbone in the area of the substitution,for example, as a beta sheet or alpha helical conformation, (b) thecharge or hydrophobicity of the molecule at the site of thesubstitution, and/or (c) the bulk of the side chain.

[0072] A “deletion” refers to a change in the amino acid or nucleotidesequence that results in the absence of one or more amino acid residuesor nucleotides.

[0073] The term “derivative” refers to a chemically modifiedpolynucleotide or polypeptide. Chemical modifications of apolynucleotide can include, for example, replacement of hydrogen by analkyl, acyl, hydroxyl, or amino group. A derivative polynucleotideencodes a polypeptide which retains at least one biological orimmunological function of the natural molecule. A derivative polypeptideis one modified by glycosylation, pegylation, or any similar processthat retains at least one biological or immunological function of thepolypeptide from which it was derived.

[0074] A “detectable label” refers to a reporter molecule or enzyme thatis capable of generating a measurable signal and is covalently ornoncovalently joined to a polynucleotide or polypeptide.

[0075] “Differential expression” refers to increased or upregulated; ordecreased, downregulated, or absent gene or protein expression,determined by comparing at least two different samples. Such comparisonsmay be carried out between, for example, a treated and an untreatedsample, or a diseased and a normal sample.

[0076] “Exon shuffling” refers to the recombination of different codingregions (exons). Since an exon may represent a structural or functionaldomain of the encoded protein, new proteins may be assembled through thenovel reassortment of stable substructures, thus allowing accelerationof the evolution of new protein functions.

[0077] A “fragment” is a unique portion of GCREC or the polynucleotideencoding GCREC which is identical in sequence to but shorter in lengththan the parent sequence. A fragment may comprise up to the entirelength of the defined sequence, minus one nucleotide/amino acid residue.For example, a fragment may comprise from 5 to 1000 contiguousnucleotides or amino acid residues. A fragment used as a probe, primer,antigen, therapeutic molecule, or for other purposes, may be at least 5,10, 15, 16, 20, 25, 30, 40, 50, 60, 75, 100, 150, 250 or at least 500contiguous nucleotides or amino acid residues in length. Fragments maybe preferentially selected from certain regions of a molecule. Forexample, a polypeptide fragment may comprise a certain length ofcontiguous amino acids selected from the first 250 or 500 amino acids(or first 25% or 50%) of a polypeptide as shown in a certain definedsequence. Clearly these lengths are exemplary, and any length that issupported by the specification, including the Sequence Listing, tables,and figures, may be encompassed by the present embodiments.

[0078] A fragment of SEQ ID NO:49-96 comprises a region of uniquepolynucleotide sequence that specifically identifies SEQ ID NO:49-96,for example, as distinct from any other sequence in the genome fromwhich the fragment was obtained. A fragment of SEQ ID NO:49-96 isuseful, for example, in hybridization and amplification technologies andin analogous methods that distinguish SEQ ID NO:49-96 from relatedpolynucleotide sequences. The precise length of a fragment of SEQ IDNO:49-96 and the region of SEQ ID NO:49-96 to which the fragmentcorresponds are routinely determinable by one of ordinary skill in theart based on the intended purpose for the fragment.

[0079] A fragment of SEQ ID NO:1-48 is encoded by a fragment of SEQ IDNO:49-96. A fragment of SEQ ID NO:1-48 comprises a region of uniqueamino acid sequence that specifically identifies SEQ ID NO:1-48. Forexample, a fragment of SEQ ID NO:1-48 is useful as an immunogenicpeptide for the development of antibodies that specifically recognizeSEQ ID NO:1-48. The precise length of a fragment of SEQ ID NO:1-48 andthe region of SEQ ID NO:1-48 to which the fragment corresponds areroutinely determinable by one of ordinary skill in the art based on theintended purpose for the fragment.

[0080] A “full length” polynucleotide sequence is one containing atleast a translation initiation codon (e.g., methionine) followed by anopen reading frame and a translation termination codon. A “full length”polynucleotide sequence encodes a “full length” polypeptide sequence.

[0081] “Homology” refers to sequence similarity or, interchangeably,sequence identity, between two or more polynucleotide sequences or twoor more polypeptide sequences.

[0082] The terms “percent identity” and “% identity,” as applied topolynucleotide sequences, refer to the percentage of residue matchesbetween at least two polynucleotide sequences aligned using astandardized algorithm. Such an algorithm may insert, in a standardizedand reproducible way, gaps in the sequences being compared in order tooptimize alignment between two sequences, and therefore achieve a moremeaningful comparison of the two sequences.

[0083] Percent identity between polynucleotide sequences may bedetermined using the default parameters of the CLUSTAL V algorithm asincorporated into the MEGALIGN version 3.12e sequence alignment program.This program is part of the LASERGENE software package, a suite ofmolecular biological analysis programs (DNASTAR, Madison Wis.). CLUSTALV is described in Higgins, D. G. and P. M. Sharp (1989) CABIOS 5:151-153and in Higgins, D. G. et al. (1992) CABIOS 8:189-191. For pairwisealignments of polynucleotide sequences, the default parameters are setas follows: Ktuple=2, gap penalty=5, window=4, and “diagonals saved”=4.The “weighted” residue weight table is selected as the default. Percentidentity is reported by CLUSTAL V as the “percent similarity” betweenaligned polynucleotide sequences.

[0084] Alternatively, a suite of commonly used and freely availablesequence comparison algorithms is provided by the National Center forBiotechnology Information (NCBI) Basic Local Alignment Search Tool(BLAST) (Altschul, S. F. et al. (1990) J. Mol. Biol. 215:403-410), whichis available from several sources, including the NCBI, Bethesda, Md.,and on the Internet at http://www.ncbi.nlm.nih.gov/BLAST/. The BLASTsoftware suite includes various sequence analysis programs including“blastn,” that is used to align a known polynucleotide sequence withother polynucleotide sequences from a variety of databases. Alsoavailable is a tool called “BLAST 2 Sequences” that is used for directpairwise comparison of two nucleotide sequences. “BLAST 2 Sequences” canbe accessed and used interactively athttp://www.ncbi.nlm.nih.gov/gorf/b12.html. The “BLAST 2 Sequences” toolcan be used for both blastn and blastp (discussed below). BLAST programsare commonly used with gap and other parameters set to default settings.For example, to compare two nucleotide sequences, one may use blastnwith the “BLAST 2 Sequences” tool Version 2.0.12 (Apr. 21, 2000) set atdefault parameters. Such default parameters may be, for example:

[0085] Matrix: BLOSUM62

[0086] Reward for match: 1

[0087] Penalty for mismatch: −2

[0088] Open Gap: 5 and Extension Gap: 2 penalties

[0089] Gap×drop-off: 50

[0090] Expect: 10

[0091] Word Size: 11

[0092] Filter: on

[0093] Percent identity may be measured over the length of an entiredefined sequence, for example, as defined by a particular SEQ ID number,or may be measured over a shorter length, for example, over the lengthof a fragment taken from a larger, defined sequence, for instance, afragment of at least 20, at least 30, at least 40, at least 50, at least70, at least 100, or at least 200 contiguous nucleotides. Such lengthsare exemplary only, and it is understood that any fragment lengthsupported by the sequences shown herein, in the tables, figures, orSequence Listing, may be used to describe a length over which percentageidentity may be measured.

[0094] Nucleic acid sequences that do not show a high degree of identitymay nevertheless encode similar amino acid sequences due to thedegeneracy of the genetic code. It is understood that changes in anucleic acid sequence can be made using this degeneracy to producemultiple nucleic acid sequences that all encode substantially the sameprotein.

[0095] The phrases “percent identity” and “% identity,” as applied topolypeptide sequences, refer to the percentage of residue matchesbetween at least two polypeptide sequences aligned using a standardizedalgorithm. Methods of polypeptide sequence alignment are well-known.Some alignment methods take into account conservative amino acidsubstitutions. Such conservative substitutions, explained in more detailabove, generally preserve the charge and_hydrophobicity at the site ofsubstitution, thus preserving the structure (and therefore function) ofthe polypeptide.

[0096] Percent identity between polypeptide sequences may be determinedusing the default parameters of the CLUSTAL V algorithm as incorporatedinto the MEGALIGN version 3.12e sequence alignment program (describedand referenced above). For pairwise alignments of polypeptide sequencesusing CLUSTAL V, the default parameters are set as follows: Ktuple=1,gap penalty=3, window=5, and “diagonals saved”=5. The PAM250 matrix isselected as the default residue weight table. As with polynucleotidealignments, the percent identity is reported by CLUSTAL V as the“percent similarity” between aligned polypeptide sequence pairs.

[0097] Alternatively the NCBI BLAST software suite may be used. Forexample, for a pairwise comparison of two polypeptide sequences, one mayuse the “BLAST 2 Sequences” tool Version 2.0.12 (Apr. 21, 2000) withblastp set at default parameters. Such default parameters may be, forexample:

[0098] Matrix: BLOSUM62

[0099] Open Gap: 11 and Extension Gap: 1 penalties

[0100] Gap×drop-off: 50

[0101] Expect: 10

[0102] Word Size: 3

[0103] Filter: on

[0104] Percent identity may be measured over the length of an entiredefined polypeptide sequence, for example, as defined by a particularSEQ ID number, or may be measured over a shorter length, for example,over the length of a fragment taken from a larger, defined polypeptidesequence, for instance, a fragment of at least 15, at least 20, at least30, at least 40, at least 50, at least 70 or at least 150 contiguousresidues. Such lengths are exemplary only, and it is understood that anyfragment length supported by the sequences shown herein, in the tables,figures or Sequence Listing, may be used to describe a length over whichpercentage identity may be measured.

[0105] “Human artificial chromosomes” (HACs) are linear microchromosomeswhich may contain DNA sequences of about 6 kb to 10 Mb in size and whichcontain all of the elements required for chromosome replication,segregation and maintenance.

[0106] The term “humanized antibody” refers to an antibody molecule inwhich the amino acid sequence in the non-antigen binding regions hasbeen altered so that the antibody more closely resembles a humanantibody, and still retains its original binding ability.

[0107] “Hybridization” refers to the process by which a polynucleotidestrand anneals with a complementary strand through base pairing underdefined hybridization conditions. Specific hybridization is anindication that two nucleic acid sequences share a high degree ofcomplementarity. Specific hybridization complexes form under permissiveannealing conditions and remain hybridized after the “washing” step(s).The washing step(s) is particularly important in determining thestringency of the hybridization process, with more stringent conditionsallowing less non-specific binding, i.e., binding between pairs ofnucleic acid strands that are not perfectly matched. Permissiveconditions for annealing of nucleic acid sequences are routinelydeterminable by one of ordinary skill in the art and may be consistentamong hybridization experiments, whereas wash conditions may be variedamong experiments to achieve the desired stringency, and thereforehybridization specificity. Permissive annealing conditions occur, forexample, at 68° C. in the presence of about 6×SSC, about 1% (w/v) SDS,and about 100 μg/ml sheared, denatured salmon sperm DNA.

[0108] Generally, stringency of hybridization is expressed, in part,with reference to the temperature under which the wash step is carriedout. Such wash temperatures are typically selected to be about 5° C. to20° C. lower than the thermal melting point (T_(m)) for the specificsequence at a defined ionic strength and pH. The T_(m) is thetemperature (under defined ionic strength and pH) at which 50% of thetarget sequence hybridizes to a perfectly matched probe. An equation forcalculating T_(m) and conditions for nucleic acid hybridization are wellknown and can be found in Sambrook, J. et al. (1989) Molecular Cloning:A Laboratory Manual, 2^(nd) ed., vol. 1-3, Cold Spring Harbor Press,Plainview N.Y.; specifically see volume 2, chapter 9.

[0109] High stringency conditions for hybridization betweenpolynucleotides of the present invention include wash conditions of 68°C. in the presence of about 0.2×SSC and about 0.1% SDS, for 1 hour.Alternatively, temperatures of about 65° C., 60° C., 55° C., or 42° C.may be used. SSC concentration may be varied from about 0.1 to 2×SSC,with SDS being present at about 0.1%. Typically, blocking reagents areused to block non-specific hybridization. Such blocking reagentsinclude, for instance, sheared and denatured salmon sperm DNA at about100-200 μg/ml. Organic solvent, such as formamide at a concentration ofabout 35-50% v/v, may also be used under particular circumstances, suchas for RNA:DNA hybridizations. Useful variations on these washconditions will be readily apparent to those of ordinary skill in theart. Hybridization, particularly under high stringency conditions, maybe suggestive of evolutionary similarity between the nucleotides. Suchsimilarity is strongly indicative of a similar role for the nucleotidesand their encoded polypeptides.

[0110] The term “hybridization complex” refers to a complex formedbetween two nucleic acid sequences by virtue of the formation ofhydrogen bonds between complementary bases. A hybridization complex maybe formed in solution (e.g., C₀t or R₀t analysis) or formed between onenucleic acid sequence present in solution and another nucleic acidsequence immobilized on a solid support (e.g., paper, membranes,filters, chips, pins or glass slides, or any other appropriate substrateto which cells or their nucleic acids have been fixed).

[0111] The words “insertion” and “addition” refer to changes in an aminoacid or nucleotide sequence resulting in the addition of one or moreamino acid residues or nucleotides, respectively.

[0112] “Immune response” can refer to conditions associated withinflammation, trauma, immune disorders, or infectious or geneticdisease, etc. These conditions can be characterized by expression ofvarious factors, e.g., cytokines, chemokines, and other signalingmolecules, which may affect cellular and systemic defense systems.

[0113] An “immunogenic fragment” is a polypeptide or oligopeptidefragment of GCREC which is capable of eliciting an immune response whenintroduced into a living organism, for example, a mammal. The term“immunogenic fragment” also includes any polypeptide or oligopeptidefragment of GCREC which is useful in any of the antibody productionmethods disclosed herein or known in the art.

[0114] The term “microarray” refers to an arrangement of a plurality ofpolynucleotides, polypeptides, or other chemical compounds on asubstrate.

[0115] The terms “element” and “array element” refer to apolynucleotide, polypeptide, or other chemical compound having a uniqueand defined position on a microarray.

[0116] The term “modulate” refers to a change in the activity of GCREC.For example, modulation may cause an increase or a decrease in proteinactivity, binding characteristics, or any other biological, functional,or immunological properties of GCREC.

[0117] The phrases “nucleic acid” and “nucleic acid sequence” refer to anucleotide, oligonucleotide, polynucleotide, or any fragment thereof.These phrases also refer to DNA or RNA of genomic or synthetic originwhich may be single-stranded or double-stranded and may represent thesense or the antisense strand, to peptide nucleic acid (PNA), or to anyDNA-like or RNA-like material.

[0118] “Operably linked” refers to the situation in which a firstnucleic acid sequence is placed in a functional relationship with asecond nucleic acid sequence. For instance, a promoter is operablylinked to a coding sequence if the promoter affects the transcription orexpression of the coding sequence. Operably linked DNA sequences may bein close proximity or contiguous and, where necessary to join twoprotein coding regions, in the same reading frame.

[0119] “Peptide nucleic acid” (PNA) refers to an antisense molecule oranti-gene agent which comprises an oligonucleotide of at least about 5nucleotides in length linked to a peptide backbone of amino acidresidues ending in lysine. The terminal lysine confers solubility to thecomposition. PNAs preferentially bind complementary single stranded DNAor RNA and stop transcript elongation, and may be pegylated to extendtheir lifespan in the cell.

[0120] “Post-translational modification” of an GCREC may involvelipidation, glycosylation, phosphorylation, acetylation, racemization,proteolytic cleavage, and other modifications known in the art. Theseprocesses may occur synthetically or biochemically. Biochemicalmodifications will vary by cell type depending on the enzymatic milieuof GCREC.

[0121] “Probe” refers to nucleic acid sequences encoding GCREC, theircomplements, or fragments thereof, which are used to detect identical,allelic or related nucleic acid sequences. Probes are isolatedoligonucleotides or polynucleotides attached to a detectable label orreporter molecule. Typical labels include radioactive isotopes, ligands,chemiluminescent agents, and enzymes. “Primers” are short nucleic acids,usually DNA oligonucleotides, which may be annealed to a targetpolynucleotide by complementary base-pairing. The primer may then beextended along the target DNA strand by a DNA polymerase enzyme. Primerpairs can be used for amplification (and identification) of a nucleicacid sequence, e.g., by the polymerase chain reaction (PCR).

[0122] Probes and primers as used in the present invention typicallycomprise at least 15 contiguous nucleotides of a known sequence. Inorder to enhance specificity, longer probes and primers may also beemployed, such as probes and primers that comprise at least 20, 25, 30,40, 50, 60, 70, 80, 90, 100, or at least 150 consecutive nucleotides ofthe disclosed nucleic acid sequences. Probes and primers may beconsiderably longer than these examples, and it is understood that anylength supported by the specification, including the tables, figures,and Sequence Listing, may be used.

[0123] Methods for preparing and using probes and primers are describedin the references, for example Sambrook, J. et al. (1989) MolecularCloning: A Laboratory Manual, 2^(nd) ed., vol. 1-3, Cold Spring HarborPress, Plainview N.Y.; Ausubel, F. M. et al. (1987) Current Protocols inMolecular Biology, Greene Publ. Assoc. & Wiley-Intersciences, New YorkN.Y.; Innis, M. et al. (1990) PCR Protocols. A Guide to Methods andApplications, Academic Press, San Diego Calif. PCR primer pairs can bederived from a known sequence, for example, by using computer programsintended for that purpose such as Primer (Version 0.5, 1991, WhiteheadInstitute for Biomedical Research, Cambridge Mass.).

[0124] Oligonucleotides for use as primers are selected using softwareknown in the art for such purpose. For example, OLIGO 4.06 software isuseful for the selection of PCR primer pairs of up to 100 nucleotideseach, and for the analysis of oligonucleotides and largerpolynucleotides of up to 5,000 nucleotides from an input polynucleotidesequence of up to 32 kilobases. Similar primer selection programs haveincorporated additional features for expanded capabilities. For example,the PrimOU primer selection program (available to the public from theGenome Center at University of Texas South West Medical Center, DallasTex.) is capable of choosing specific primers from megabase sequencesand is thus useful for designing primers on a genome-wide scope. ThePrimer3 primer selection program (available to the public from theWhitehead Institute/MIT Center for Genome Research, Cambridge Mass.)allows the user to input a “mispriming library,” in which sequences toavoid as primer binding sites are user-specified. Primer3 is useful, inparticular, for the selection of oligonucleotides for microarrays. (Thesource code for the latter two primer selection programs may also beobtained from their respective sources and modified to meet the user'sspecific needs.) The PrimeGen program (available to the public from theUK Human Genome Mapping Project Resource Centre, Cambridge UK) designsprimers based on multiple sequence alignments, thereby allowingselection of primers that hybridize to either the most conserved orleast conserved regions of aligned nucleic acid sequences. Hence, thisprogram is useful for identification of both unique and conservedoligonucleotides and polynucleotide fragments. The oligonucleotides andpolynucleotide fragments identified by any of the above selectionmethods are useful in hybridization technologies, for example, as PCR orsequencing primers, microarray elements, or specific probes to identifyfully or partially complementary polynucleotides in a sample of nucleicacids. Methods of oligonucleotide selection are not limited to thosedescribed above.

[0125] A “recombinant nucleic acid” is a sequence that is not naturallyoccurring or has a sequence that is made by an artificial combination oftwo or more otherwise separated segments of sequence. This artificialcombination is often accomplished by chemical synthesis or, morecommonly, by the artificial manipulation of isolated segments of nucleicacids, e.g., by genetic engineering techniques such as those describedin Sambrook, supra. The term recombinant includes nucleic acids thathave been altered solely by addition, substitution, or deletion of aportion of the nucleic acid. Frequently, a recombinant nucleic acid mayinclude a nucleic acid sequence operably linked to a promoter sequence.Such a recombinant nucleic acid may be part of a vector that is used,for example, to transform a cell.

[0126] Alternatively, such recombinant nucleic acids may be part of aviral vector, e.g., based on a vaccinia virus, that could be use tovaccinate a mammal wherein the recombinant nucleic acid is expressed,inducing a protective immunological response in the mammal.

[0127] A “regulatory element” refers to a nucleic acid sequence usuallyderived from untranslated regions of a gene and includes enhancers,promoters, introns, and 5′ and 3′ untranslated regions (UTRs).Regulatory elements interact with host or viral proteins which controltranscription, translation, or RNA stability.

[0128] “Reporter molecules” are chemical or biochemical moieties usedfor labeling a nucleic acid, amino acid, or antibody. Reporter moleculesinclude radionuclides; enzymes; fluorescent, chemiluminescent, orchromogenic agents; substrates; cofactors; inhibitors; magneticparticles; and other moieties known in the art.

[0129] An “RNA equivalent,” in reference to a DNA sequence, is composedof the same linear sequence of nucleotides as the reference DNA sequencewith the exception that all occurrences of the nitrogenous base thymineare replaced with uracil, and the sugar backbone is composed of riboseinstead of deoxyribose.

[0130] The term “sample” is used in its broadest sense. A samplesuspected of containing GCREC, nucleic acids encoding GCREC, orfragments thereof may comprise a bodily fluid; an extract from a cell,chromosome, organelle, or membrane isolated from a cell; a cell; genomicDNA, RNA, or cDNA, in solution or bound to a substrate; a tissue; atissue print; etc.

[0131] The terms “specific binding” and “specifically binding” refer tothat interaction between a protein or peptide and an agonist, anantibody, an antagonist, a small molecule, or any natural or syntheticbinding composition. The interaction is dependent upon the presence of aparticular structure of the protein, e.g., the antigenic determinant orepitope, recognized by the binding molecule. For example, if an antibodyis specific for epitope “A,” the presence of a polypeptide comprisingthe epitope A, or the presence of free unlabeled A, in a reactioncontaining free labeled A and the antibody will reduce the amount oflabeled A that binds to the antibody.

[0132] The term “substantially purified” refers to nucleic acid or aminoacid sequences that are removed from their natural environment and areisolated or separated, and are at least 60% free, preferably at least75% free, and most preferably at least 90% free from other componentswith which they are naturally associated.

[0133] A “substitution” refers to the replacement of one or more aminoacid residues or nucleotides by different amino acid residues ornucleotides, respectively.

[0134] “Substrate” refers to any suitable rigid or semi-rigid supportincluding membranes, filters, chips, slides, wafers, fibers, magnetic ornonmagnetic beads, gels, tubing, plates, polymers, microparticles andcapillaries. The substrate can have a variety of surface forms, such aswells, trenches, pins, channels and pores, to which polynucleotides orpolypeptides are bound.

[0135] A “transcript image” or “expression profile” refers to thecollective pattern of gene expression by a particular cell type ortissue under given conditions at a given time.

[0136] “Transformation” describes a process by which exogenous DNA isintroduced into a recipient cell. Transformation may occur under naturalor artificial conditions according to various methods well known in theart, and may rely on any known method for the insertion of foreignnucleic acid sequences into a prokaryotic or eukaryotic host cell. Themethod for transformation is selected based on the type of host cellbeing transformed and may include, but is not limited to, bacteriophageor viral infection, electroporation, heat shock, lipofection, andparticle bombardment. The term “transformed cells” includes stablytransformed cells in which the inserted DNA is capable of replicationeither as an autonomously replicating plasmid or as part of the hostchromosome, as well as transiently transformed cells which express theinserted DNA or RNA for limited periods of time.

[0137] A “transgenic organism,” as used herein, is any organism,including but not limited to animals and plants, in which one or more ofthe cells of the organism contains heterologous nucleic acid introducedby way of human intervention, such as by transgenic techniques wellknown in the art. The nucleic acid is introduced into the cell, directlyor indirectly by introduction into a precursor of the cell, by way ofdeliberate genetic manipulation, such as by microinjection or byinfection with a recombinant virus. The term genetic manipulation doesnot include classical cross-breeding, or in vitro fertilization, butrather is directed to the introduction of a recombinant DNA molecule.The transgenic organisms contemplated in accordance with the presentinvention include bacteria, cyanobacteria, fungi, plants and animals.The isolated DNA of the present invention can be introduced into thehost by methods known in the art, for example infection, transfection,transformation or transconjugation. Techniques for transferring the DNAof the present invention into such organisms are widely known andprovided in references such as Sambrook et al. (1989), supra.

[0138] A “variant” of a particular nucleic acid sequence is defined as anucleic acid sequence having at least 40% sequence identity to theparticular nucleic acid sequence over a certain length of one of thenucleic acid sequences using blastn with the “BLAST 2 Sequences” toolVersion 2.0.9 (May 7, 1999) set at default parameters. Such a pair ofnucleic acids may show, for example, at least 50%, at least 60%, atleast 70%, at least 80%, at least 85%,.at least 90%, at least 91%, atleast 92%, at least 93%, at least 94%, at least 95%, at least 96%, atleast 97%, at least 98%, or at least 99% or greater sequence identityover a certain defined length. A variant may be described as, forexample, an “allelic” (as defined above), “splice,” “species,” or“polymorphic” variant. A splice variant may have significant identity toa reference molecule, but will generally have a greater or lesser numberof polynucleotides due to alternate splicing of exons during mRNAprocessing. The corresponding polypeptide may possess additionalfunctional domains or lack domains that are present in the referencemolecule. Species variants are polynucleotide sequences that vary fromone species to another. The resulting polypeptides will generally havesignificant amino acid identity relative to each other. A polymorphicvariant is a variation in the polynucleotide sequence of a particulargene between individuals of a given species. Polymorphic variants alsomay encompass “single nucleotide polymorphisms” (SNPs) in which thepolynucleotide sequence varies by one nucleotide base. The presence ofSNPs may be indicative of, for example, a certain population, a diseasestate, or a propensity for a disease state.

[0139] A “variant” of a particular polypeptide sequence is defined as apolypeptide sequence having at least 40% sequence identity to theparticular polypeptide sequence over a certain length of one of thepolypeptide sequences using blastp with the “BLAST 2 Sequences” toolVersion 2.0.9 (May 07, 1999) set at default parameters. Such a pair ofpolypeptides may show, for example, at least 50%, at least 60%, at least70%, at least 80%, at least 90%, at least 91%, at least 92%, at least93%, at least 94%, at least 95%, at least 96%, at least 97%, at least98%, or at least 99% or greater sequence identity over a certain definedlength of one of the polypeptides.

[0140] The Invention

[0141] The invention is based on the discovery of new human G-proteincoupled receptors (GCREC), the polynucleotides encoding GCREC, and theuse of these compositions for the diagnosis, treatment, or prevention ofcell proliferative, neurological, cardiovascular, gastrointestinal,autoimmune/inflammatory, and metabolic disorders, and viral infections.

[0142] Table 1 summarizes the nomenclature for the full lengthpolynucleotide and polypeptide sequences of the invention. Eachpolynucleotide and its corresponding polypeptide are correlated to asingle Incyte project identification number (Incyte Project ID). Eachpolypeptide sequence, is denoted by both a polypeptide sequenceidentification number (Polypeptide SEQ ID NO:) and an Incyte polypeptidesequence number (Incyte Polypeptide ID) as shown. Each polynucleotidesequence is denoted by both a polynucleotide sequence identificationnumber (Polynucleotide SEQ ID NO:) and an Incyte polynucleotideconsensus sequence number (Incyte Polynucleotide ID) as shown.

[0143] Table 2 shows sequences with homology to the polypeptides of theinvention as identified by BLAST analysis against the GenBank protein(genpept) database. Columns 1 and 2 show the polypeptide sequenceidentification number (Polypeptide SEQ ID NO:) and the correspondingIncyte polypeptide sequence number (Incyte Polypeptide ID) forpolypeptides of the invention. Column 3 shows the GenBank identificationnumber (GenBank ID NO:) of the nearest GenBank homolog. Column 4 showsthe probability scores for the matches between each polypeptide and itshomolog(s). Column 5 shows the annotation of the GenBank homolog(s)along with relevant citations where applicable, all of which areexpressly incorporated by reference herein.

[0144] Table 3 shows various structural features of the polypeptides ofthe invention. Columns 1 and 2 show the polypeptide sequenceidentification number (SEQ ID NO:) and the corresponding Incytepolypeptide sequence number (Incyte Polypeptide ID) for each polypeptideof the invention. Column 3 shows the number of amino acid residues ineach polypeptide. Column 4 shows potential phosphorylation sites, andcolumn 5 shows potential glycosylation sites, as determined by theMOTIFS program of the GCG sequence analysis software package (GeneticsComputer Group, Madison Wis.). Column 6 shows amino acid residuescomprising signature sequences, domains, and motifs. Column 7 showsanalytical methods for protein structure/function analysis and in somecases, searchable databases to which the analytical methods wereapplied.

[0145] Together, Tables 2 and 3 summarize the properties of polypeptidesof the invention, and these properties establish that the claimedpolypeptides are G-protein coupled receptors. For example, SEQ ID NO:1is 28% identical, from residue 1370 to residue K680, to chicken ovarianfollicle-stimulating hormone receptor (GenBank ID g1256414) and 51%identical, from residue L136 to residue E702, to human leucine-richrepeat-containing G protein-coupled receptor 7 (GenBank ID g10441730) asdetermined by the Basic Local Alignment Search Tool (BLAST). (See Table2.) The BLAST probability scores are 7.5e-41 and 1.4e-153, respectively,indicating the probabilities of obtaining the observed polypeptidesequence alignments by chance. SEQ ID NO:1 also contains a rhodopsinfamily 7-transmembrane receptor domain, 9 leucine rich repeats, and alow-density lipoprotein receptor domain, as determined by searching forstatistically significant matches in the hidden Markov model (HMM)-basedPFAM database of conserved protein family domains. (See Table 3.) Datafrom BLIMPS, MOTIFS, and PROFILESCAN analyses provide furthercorroborative evidence that SEQ ID NO:1 is a G-protein coupled hormonereceptor with leucine-rich repeats. In a further example, SEQ ID NO:2 is29% identical, from residue V203 to residue S871, to rat seventransmembrane receptor Ig-Hepta (GenBank ID g5525078) with a BLASTprobability score of 6.7e-67. (See Table 2.) SEQ ID NO:2 also contains a7 transmembrane receptor (secretin family) domain and alatrophilin/CL-1-like GPS domain as determined by searching forstatistically significant matches in the HMM-based PFAM database ofconserved protein family domains. (See Table 3.) Data from BLIMPS andMOTIFS analyses provide further corroborative evidence that SEQ ID NO:2is a secretin-like GPCR. In a further example, SEQ ID NO:3 is 36%identical, from residue L56 to residue T243, to human small cellvasopressin subtype 1b receptor (GenBank ID g2613125) with a BLASTprobability score of 9.7e-41. (See Table 2.) SEQ ID NO:3 also contains a7 transmembrane receptor (rhodopsin family) domain as determined bysearching for statistically significant matches in the HMM-based PFAMdatabase of conserved protein family domains. (See Table 3.) Data fromBLIMPS, MOTIFS, and PROFILESCAN analyses provide further corroborativeevidence that SEQ ID NO:3 is a vasopressin receptor. In a furtherexample, SEQ ID NO:4 is 23% identical, from residue S30 to residue Q301,to human cysteinyl leukotriene receptor (GenBank ID g5359718) with aBLAST probability score of 4.5e-21. (See Table 2.) Data from BLIMPS andadditional BLAST analyses provide corroborative evidence that SEQ IDNO:4 is a G-protein coupled receptor. In a further example, SEQ ID NO:8is 99% identical, from residue M1 to residue V345, to human orphanG-protein coupled receptor (GenBank ID g8118040) with a BLASTprobability score of 2.9e-186. (See Table 2.) SEQ ID NO:8 also containsa 7 transmembrane receptor metabotropic glutamate family domain asdetermined by searching for statistically significant matches in theHMM-based PFAM database of conserved protein family domains. (See Table3.) Data from BLAST analysis provide further corroborative evidence thatSEQ ID NO:8 is a G-protein coupled receptor. In a further example,example, SEQ ID NO:10 is 64% identical, from residue N5 to residue I307,to Mus musculus odorant receptor S46 (GenBank ID g4680268)with a BLASTprobability score of 6.2e-111. (See Table 2.) SEQ ID NO:10 also containsa 7-transmembrane receptor (rhodopsin family) domain as determined bysearching for statistically significant matches in the HMM-based PFAMdatabase of conserved protein family domains. (See Table 3.) Data fromBLIMPS, MOTIFS, and PROFILESCAN analyses provide further corroborativeevidence that SEQ ID NO:10 is an olfactory GPCR. SEQ ID NO:5-7, SEQ IDNO:9, SEQ ID NO:11-44, and SEQ ID NO:45-48 were analyzed and annotatedin a similar manner. The algorithms and parameters for the analysis ofSEQ ID NO:1-48 are described in Table 7.

[0146] As shown in Table 4, the full length polynucleotide sequences ofthe present invention were assembled using cDNA sequences or coding(exon) sequences derived from genomic DNA, or any combination of thesetwo types of sequences. Column 1 lists the polynucleotide sequenceidentification number (Polynucleotide SEQ ID NO:), the correspondingIncyte polynucleotide consensus sequence number (Incyte ID) for eachpolynucleotide of the invention, and the length of each polynucleotidesequence in basepairs. Column 2 shows the nucleotide start (5′) and stop(3′) positions of the cDNA and/or genomic sequences used to assemble thefull length polynucleotide sequences of the invention, and of fragmentsof the polynucleotide sequences which are useful, for example, inhybridization or amplification technologies that identify SEQ IDNO:49-96 or that distinguish between SEQ ID NO:49-96 and relatedpolynucleotide sequences.

[0147] The polynucleotide fragments described in Column 2 of Table 4 mayrefer specifically, for example, to Incyte cDNAs derived fromtissue-specific cDNA libraries or from pooled cDNA libraries.Alternatively, the polynucleotide fragments described in column 2 mayrefer to GenBank cDNAs or ESTs which contributed to the assembly of thefull length polynucleotide sequences. In addition, the polynucleotidefragments described in column 2 may identify sequences derived from theENSEMBL (The Sanger Centre, Cambridge, UK) database (i.e., thosesequences including the designation “ENST”). Alternatively, thepolynucleotide fragments described in column 2 may be derived from theNCBI RefSeq Nucleotide Sequence Records Database (i.e., those sequencesincluding the designation “NM” or “NT”) or the NCBI RefSeq ProteinSequence Records (i.e., those sequences including the designation “NP”).Alternatively, the polynucleotide fragments described in column 2 mayrefer to assemblages of both cDNA and Genscan-predicted exons broughttogether by an “exon stitching” algorithm. For example, a polynucleotidesequence identified as FL_XXXXXX_N₁ _(—) N₂ _(—) YYYYY_N₃ _(—) N₄represents a “stitched” sequence in which XXXXXX is the identificationnumber of the cluster of sequences to which the algorithm was applied,and YYYYY is the number of the prediction generated by the algorithm,and N_(1,2,3 . . .) , if present, represent specific exons that may havebeen manually edited during analysis (See Example V). Alternatively, thepolynucleotide fragments in column 2 may refer to assemblages of exonsbrought together by an “exon-stretching” algorithm. For example, apolynucleotide sequence identified as FLXXXXXX_gAAAAA_gBBBBB_(—)1_N is a“stretched” sequence, with XXXXXX being the Incyte projectidentification number, gAAAAA being the GenBank identification number ofthe human genomic sequence to which the “exon-stretching” algorithm wasapplied, gBBBBB being the GenBank identification number or NCBI RefSeqidentification number of the nearest GenBank protein homolog, and Nreferring to specific exons (See Example V). In instances where a RefSeqsequence was used as a protein homolog for the “exon-stretching”algorithm, a RefSeq identifier (denoted by “NM,” “NP,” or “NT”) may beused in place of the GenBank identifier (i.e., gBBBBB).

[0148] Alternatively, a prefix identifies component sequences that werehand-edited, predicted from genomic DNA sequences, or derived from acombination of sequence analysis methods. The following Table listsexamples of component sequence prefixes and corresponding sequenceanalysis methods associated with the prefixes (see Example IV andExample V). Prefix Type of analysis and/or examples of programs GNN,GFG, Exon prediction from genomic sequences using, for ENST example,GENSCAN (Stanford University, CA, USA) or FGENES (Computer GenomicsGroup, The Sanger Centre, Cambridge, UK). GBI Hand-edited analysis ofgenomic sequences. FL Stitched or stretched genomic sequences (seeExample V). INCY Full length transcript and exon prediction from mappingof EST sequences to the genome. Genomic location and EST compositiondata are combined to predict the exons and resulting transcript.

[0149] In some cases, Incyte cDNA coverage redundant with the sequencecoverage shown in Table 4 was obtained to confirm the final consensuspolynucleotide sequence, but the relevant Incyte cDNA identificationnumbers are not shown.

[0150] Table 5 shows the representative cDNA libraries for those fulllength polynucleotide sequences which were assembled using Incyte cDNAsequences. The representative cDNA library is the Incyte cDNA librarywhich is most frequently represented by the Incyte cDNA sequences whichwere used to assemble and confirm the above polynucleotide sequences.The tissues and vectors which were used to construct the cDNA librariesshown in Table 5 are described in Table 6.

[0151] The invention also encompasses GCREC variants. A preferred GCRECvariant is one which has at least about 80%, or alternatively at leastabout 90%, or alternatively at least about 95%, or even at least about99% amino acid sequence identity to the GCREC amino acid sequence, andwhich contains at least one functional or structural characteristic ofGCREC.

[0152] The invention also encompasses polynucleotides which encodeGCREC. In a particular embodiment, the invention encompasses apolynucleotide sequence comprising a sequence selected from the groupconsisting of SEQ ID NO:49-96, which encodes GCREC. The polynucleotidesequences of SEQ ID NO:49-96, as presented in the Sequence Listing,embrace the equivalent RNA sequences, wherein occurrences of thenitrogenous base thymine are replaced with uracil, and the sugarbackbone is composed of ribose instead of deoxyribose.

[0153] The invention also encompasses a variant of a polynucleotidesequence encoding GCREC. In particular, such a variant polynucleotidesequence will have at least about 70%, or alternatively at least about85%, or alternatively at least about 95%, or even at least about 99%polynucleotide sequence identity to the polynucleotide sequence encodingGCREC. A particular aspect of the invention encompasses a variant of apolynucleotide sequence comprising a sequence selected from the groupconsisting of SEQ ID NO:49-96 which has at least about 70%, oralternatively at least about 85%, or alternatively at least about 95%,or even at least about 99% polynucleotide sequence identity to a nucleicacid sequence selected from the group consisting of SEQ ID NO:49-96. Anyone of the polynucleotide variants described above can encode an aminoacid sequence which contains at least one functional or structuralcharacteristic of GCREC.

[0154] In addition, or in the alternative, a polynucleotide variant ofthe invention is a splice variant of a polynucleotide sequence encodingGCREC. A splice variant may have portions which have significantsequence identity to the polynucleotide sequence encoding GCREC, butwill generally have a greater or lesser number of polynucleotides due toadditions or deletions of blocks of sequence arising from alternatesplicing of exons during mRNA processing. A splice variant may have lessthan about 70%, or alternatively less than about 60%, or alternativelyless than about 50% polynucleotide sequence identity to thepolynucleotide sequence encoding GCREC over its entire length; however,portions of the splice variant will have at least about 70%, oralternatively at least about 85%, or alternatively at least about 95%,or alternatively 100% polynucleotide sequence identity to portions ofthe polynucleotide sequence encoding GCREC. Any one of the splicevariants described above can encode an amino acid sequence whichcontains at least one functional or structural characteristic of GCREC.

[0155] It will be appreciated by those skilled in the art that as aresult of the degeneracy of the genetic code, a multitude ofpolynucleotide sequences encoding GCREC, some bearing minimal similarityto the polynucleotide sequences of any known and naturally occurringgene, may be produced. Thus, the invention contemplates each and everypossible variation of polynucleotide sequence that could be made byselecting combinations based on possible codon choices. Thesecombinations are made in accordance with the standard triplet geneticcode as applied to the polynucleotide sequence of naturally occurringGCREC, and all such variations are to be considered as beingspecifically disclosed.

[0156] Although nucleotide sequences which encode GCREC and its variantsare generally capable of hybridizing to the nucleotide sequence of thenaturally occurring GCREC under appropriately selected conditions ofstringency, it may be advantageous to produce nucleotide sequencesencoding GCREC or its derivatives possessing a substantially differentcodon usage, e.g., inclusion of non-naturally occurring codons. Codonsmay be selected to increase the rate at which expression of the peptideoccurs in a particular prokaryotic or eukaryotic host in accordance withthe frequency with which particular codons are utilized by the host.Other reasons for substantially altering the nucleotide sequenceencoding GCREC and its derivatives without altering the encoded aminoacid sequences include the production of RNA transcripts having moredesirable properties, such as a greater half-life, than transcriptsproduced from the naturally occurring sequence.

[0157] The invention also encompasses production of DNA sequences whichencode GCREC and GCREC derivatives, or fragments thereof, entirely bysynthetic chemistry. After production, the synthetic sequence may beinserted into any of the many available expression vectors and cellsystems using reagents well known in the art. Moreover, syntheticchemistry may be used to introduce mutations into a sequence encodingGCREC or any fragment thereof.

[0158] Also encompassed by the invention are polynucleotide sequencesthat are capable of hybridizing to the claimed polynucleotide sequences,and, in particular, to those shown in SEQ ID NO:49-96 and fragmentsthereof under various conditions of stringency. (See, e.g., Wahl, G. M.and S. L. Berger (1987) Methods Enzymol. 152:399-407; Kimmel, A. R.(1987) Methods Enzymol. 152:507-511.) Hybridization conditions,including annealing and wash conditions, are described in “Definitions.”

[0159] Methods for DNA sequencing are well known in the art and may beused to practice any of the embodiments of the invention. The methodsmay employ such enzymes as the Klenow fragment of DNA polymerase I,SEQUENASE (US Biochemical, Cleveland Ohio), Taq polymerase (AppliedBiosystems), thermostable T7 polymerase (Amersham Pharmacia Biotech,Piscataway N.J.), or combinations of polymerases and proofreadingexonucleases such as those found in the ELONGASE amplification system(Life Technologies, Gaithersburg Md.). Preferably, sequence preparationis automated with machines such as the MICROLAB 2200 liquid transfersystem (Hamilton, Reno Nev.), PTC200 thermal cycler (MJ Research,Watertown Mass.) and ABI CATALYST 800 thermal cycler (AppliedBiosystems). Sequencing is then carried out using either the ABI 373 or377 DNA sequencing system (Applied Biosystems), the MEGABACE 1000 DNAsequencing system (Molecular Dynamics, Sunnyvale Calif.), or othersystems known in the art. The resulting sequences are analyzed using avariety of algorithms which are well known in the art. (See, e.g.,Ausubel, F. M. (1997) Short Protocols in Molecular Biology, John Wiley &Sons, New York N.Y., unit 7.7; Meyers, R. A. (1995) Molecular Biologyand Biotechnology, Wiley VCH, New York N.Y., pp. 856-853.)

[0160] The nucleic acid sequences encoding GCREC may be extendedutilizing a partial nucleotide sequence and employing various PCR-basedmethods known in the art to detect upstream sequences, such as promotersand regulatory elements. For example, one method which may be employed,restriction-site PCR, uses universal and nested primers to amplifyunknown sequence from genomic DNA within a cloning vector. (See, e.g.,Sarkar, G. (1993) PCR Methods Applic. 2:318-322.) Another method,inverse PCR, uses primers that extend in divergent directions to amplifyunknown sequence from a circularized template. The template is derivedfrom restriction fragments comprising a known genomic locus andsurrounding sequences. (See, e.g., Triglia, T. et al. (1988) NucleicAcids Res. 16:8186.) A third method, capture PCR, involves PCRamplification of DNA fragments adjacent to known sequences in human andyeast artificial chromosome DNA. (See, e.g., Lagerstrom, M. et al.(1991) PCR Methods Applic. 1:111-119.) In this method, multiplerestriction enzyme digestions and ligations may be used to insert anengineered double-stranded sequence into a region of unknown sequencebefore performing PCR. Other methods which may be used to retrieveunknown sequences are known in the art. (See, e.g., Parker, J. D. et al.(1991) Nucleic Acids Res. 19:3055-3060). Additionally, one may use PCR,nested primers, and PROMOTERFINDER libraries (Clontech, Palo AltoCalif.) to walk genomic DNA. This procedure avoids the need to screenlibraries and is useful in finding intron/exon junctions. For allPCR-based methods, primers may be designed using commercially availablesoftware, such as OLIGO 4.06 primer analysis software (NationalBiosciences, Plymouth Minn.) or another appropriate program, to be about22 to 30 nucleotides in length, to have a GC content of about 50% ormore, and to anneal to the template at temperatures of about 68° C. to72° C.

[0161] When screening for full length cDNAs, it is preferable to uselibraries that have been size-selected to include larger cDNAs. Inaddition, random-primed libraries, which often include sequencescontaining the 5′ regions of genes, are preferable for situations inwhich an oligo d(T) library does not yield a full-length cDNA. Genomiclibraries may be useful for extension of sequence into 5′non-transcribed regulatory regions.

[0162] Capillary electrophoresis systems which are commerciallyavailable may be used to analyze the size or confirm the nucleotidesequence of sequencing or PCR products. In particular, capillarysequencing may employ flowable polymers for electrophoretic separation,four different nucleotide-specific, laser-stimulated fluorescent dyes,and a charge coupled device camera for detection of the emittedwavelengths. Output/light intensity may be converted to electricalsignal using appropriate software (e.g., GENOTYPER and SEQUENCENAVIGATOR, Applied Biosystems), and the entire process from loading ofsamples to computer analysis and electronic data display may be computercontrolled. Capillary electrophoresis is especially preferable forsequencing small DNA fragments which may be present in limited amountsin a particular sample.

[0163] In another embodiment of the invention, polynucleotide sequencesor fragments thereof which encode GCREC may be cloned in recombinant DNAmolecules that direct expression of GCREC, or fragments or functionalequivalents thereof, in appropriate host cells. Due to the inherentdegeneracy of the genetic code, other DNA sequences which encodesubstantially the same or a functionally equivalent amino acid sequencemay be produced and used to express GCREC.

[0164] The nucleotide sequences of the present invention can beengineered using methods generally known in the art in order to alterGCREC-encoding sequences for a variety of purposes including, but notlimited to, modification of the cloning, processing, and/or expressionof the gene product. DNA shuffling by random fragmentation and PCRreassembly of gene fragments and synthetic oligonucleotides may be usedto engineer the nucleotide sequences. For example,oligonucleotide-mediated site-directed mutagenesis may be used tointroduce mutations that create new restriction sites, alterglycosylation patterns, change codon preference, produce splicevariants, and so forth.

[0165] The nucleotides of the present invention may be subjected to DNAshuffling techniques such as MOLECULARBREEDING (Maxygen Inc., SantaClara Calif.; described in U.S. Pat. No. 5,837,458; Chang, C. -C. et al.(1999) Nat. Biotechnol. 17:793-797; Christians, F. C. et al. (1999) Nat.Biotechnol. 17:259-264; and Crameri, A. et al. (1996) Nat. Biotechnol.14:315-319) to alter or improve the biological properties of GCREC, suchas its biological or enzymatic activity or its ability to bind to othermolecules or compounds. DNA shuffling is a process by which a library ofgene variants is produced using PCR-mediated recombination of genefragments. The library is then subjected to selection or screeningprocedures that identify those gene variants with the desiredproperties. These preferred variants may then be pooled and furthersubjected to recursive rounds of DNA shuffling and selection/screening.Thus, genetic diversity is created through “artificial” breeding andrapid molecular evolution. For example, fragments of a single genecontaining random point mutations may be recombined, screened, and thenreshuffled until the desired properties are optimized. Alternatively,fragments of a given gene may be recombined with fragments of homologousgenes in the same gene family, either from the same or differentspecies, thereby maximizing the genetic diversity of multiple naturallyoccurring genes in a directed and controllable manner.

[0166] In another embodiment, sequences encoding GCREC may besynthesized, in whole or in part, using chemical methods well known inthe art. (See, e.g., Caruthers, M. H. et al. (1980) Nucleic Acids Symp.Ser. 7:215-223; and Horn, T. et al. (1980) Nucleic Acids Symp. Ser.7:225-232.) Alternatively, GCREC itself or a fragment thereof may besynthesized using chemical methods. For example, peptide synthesis canbe performed using various solution-phase or solid-phase techniques.(See, e.g., Creighton, T. (1984) Proteins, Structures and MolecularProperties, WH Freeman, New York N.Y., pp. 55-60; and Roberge, J. Y. etal. (1995) Science 269:202-204.) Automated synthesis may be achievedusing the ABI 431A peptide synthesizer (Applied Biosystems).Additionally, the amino acid sequence of GCREC, or any part thereof, maybe altered during direct synthesis and/or combined with sequences fromother proteins, or any part thereof, to produce a variant polypeptide ora polypeptide having a sequence of a naturally occurring polypeptide.

[0167] The peptide may be substantially purified by preparative highperformance liquid chromatography. (See, e.g., Chiez, R. M. and F. Z.Regnier (1990) Methods Enzymol. 182:392-421.) The composition of thesynthetic peptides may be confirmed by amino acid analysis or bysequencing. (See, e.g., Creighton, supra, pp. 28-53.)

[0168] In order to express a biologically active GCREC, the nucleotidesequences encoding GCREC or derivatives thereof may be inserted into anappropriate expression vector, i.e., a vector which contains thenecessary elements for transcriptional and translational control of theinserted coding sequence in a suitable host. These elements includeregulatory sequences, such as enhancers, constitutive and induciblepromoters, and 5′ and 3′ untranslated regions in the vector and inpolynucleotide sequences encoding GCREC. Such elements may vary in theirstrength and specificity. Specific initiation signals may also be usedto achieve more efficient translation of sequences encoding GCREC. Suchsignals include the ATG initiation codon and adjacent sequences, e.g.the Kozak sequence. In cases where sequences encoding GCREC and itsinitiation codon and upstream regulatory sequences are inserted into theappropriate expression vector, no additional transcriptional ortranslational control signals may be needed. However, in cases whereonly coding sequence, or a fragment thereof, is inserted, exogenoustranslational control signals including an in-frame ATG initiation codonshould be provided by the vector. Exogenous translational elements andinitiation codons may be of various origins, both natural and synthetic.The efficiency of expression may be enhanced by the inclusion ofenhancers appropriate for the particular host cell system used. (See,e.g., Scharf, D. et al. (1994) Results Probl. Cell Differ. 20:125-162.)

[0169] Methods which are well known to those skilled in the art may beused to construct expression vectors containing sequences encoding GCRECand appropriate transcriptional and translational control elements.These methods include in vitro recombinant DNA techniques, synthetictechniques, and in vivo genetic recombination. (See, e.g., Sambrook, J.et al. (1989) Molecular Cloning, A Laboratory Manual, Cold Spring HarborPress, Plainview N.Y., ch. 4, 8, and 16-17; Ausubel, F. M. et al. (1995)Current Protocols in Molecular Biology, John Wiley & Sons, New YorkN.Y., ch. 9, 13, and 16.)

[0170] A variety of expression vector/host systems may be utilized tocontain and express sequences encoding GCREC. These include, but are notlimited to, microorganisms such as bacteria transformed with recombinantbacteriophage, plasmid, or cosmid DNA expression vectors; yeasttransformed with yeast expression vectors; insect cell systems infectedwith viral expression vectors (e.g., baculovirus); plant cell systemstransformed with viral expression vectors (e.g., cauliflower mosaicvirus, CaMV, or tobacco mosaic virus, TMV) or with bacterial expressionvectors (e.g., Ti or pBR322 plasmids); or animal cell systems. (See,e.g., Sambrook, supra; Ausubel, supra; Van Heeke, G. and S. M. Schuster(1989) J. Biol. Chem. 264:5503-5509; Engelhard, E. K. et al. (1994)Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum.Gene Ther. 7:1937-1945; Takamatsu, N. (1987) EMBO S J. 6:307-311; TheMcGraw Hill Yearbook of Science and Technology (1992) McGraw Hill, NewYork N.Y., pp. 191-196; Logan, J. and T. Shenk (1984) Proc. Natl. Acad.Sci. USA 81:3655-3659; and Harrington, J. J. et al. (1997) Nat. Genet.15:345-355.) Expression vectors derived from retroviruses, adenoviruses,or herpes or vaccinia viruses, or from various bacterial plasmids, maybe used for delivery of nucleotide sequences to the targeted organ,tissue, or cell population. (See, e.g., Di Nicola, M. et al. (1998)Cancer Gen. Ther. 5(6):350-356; Yu, M. et al. (1993) Proc. Natl. Acad.Sci. USA 90(13):6340-6344; Buller, R. M. et al. (1985) Nature317(6040):813-815; McGregor, D. P. et al. (1994) Mol. Immunol.31(3):219-226; and Verma, I. M. and N. Somia (1997) Nature 389:239-242.)The invention is not limited by the host cell employed.

[0171] In bacterial systems, a number of cloning and expression vectorsmay be selected depending upon the use intended for polynucleotidesequences encoding GCREC. For example, routine cloning, subcloning, andpropagation of polynucleotide sequences encoding GCREC can be achievedusing a multifunctional E. coli vector such as PBLUESCRIPT (Stratagene,La Jolla Calif.) or PSPORT1 plasmid (Life Technologies). Ligation ofsequences encoding GCREC into the vector's multiple cloning sitedisrupts the lacZ gene, allowing a colorimetric screening procedure foridentification of transformed bacteria containing recombinant molecules.In addition, these vectors may be useful for in vitro transcription,dideoxy sequencing, single strand rescue with helper phage, and creationof nested deletions in the cloned sequence. (See, e.g., Van Heeke, G.and S. M. Schuster (1989) J. Biol. Chem. 264:5503-5509.) When largequantities of GCREC are needed, e.g. for the production of antibodies,vectors which direct high level expression of GCREC may be used. Forexample, vectors containing the strong, inducible SP6 or T7bacteriophage promoter may be used.

[0172] Yeast expression systems may be used for production of GCREC. Anumber of vectors containing constitutive or inducible promoters, suchas alpha factor, alcohol oxidase, and PGH promoters, may be used in theyeast Saccharomyces cerevisiae or Pichia pastoris. In addition, suchvectors direct either the secretion or intracellular retention ofexpressed proteins and enable integration of foreign sequences into thehost genome for stable propagation. (See, e.g., Ausubel, 1995, supra;Bitter, G. A. et al. (1987) Methods Enzymol. 153:516-544; and Scorer, C.A. et al. (1994) Bio/Technology 12:181-184.)

[0173] Plant systems may also be used for expression of GCREC.Transcription of sequences encoding GCREC may be driven by viralpromoters, e.g., the 35S and 19S promoters of CaMV used alone or incombination with the omega leader sequence from TMV (Takamatsu, N.(1987) EMBO J. 6:307-311). Alternatively, plant promoters such as thesmall subunit of RUBISCO or heat shock promoters may be used. (See,e.g., Coruzzi, G. et al. (1984) EMBO J. 3:1671-1680; Broglie, R. et al.(1984) Science 224:838-843; and Winter, J. et al. (1991) Results Probl.Cell Differ. 17:85-105.) These constructs can be introduced into plantcells by direct DNA transformation or pathogen-mediated transfection.(See, e.g., The McGraw Hill Yearbook of Science and Technology (1992)McGraw Hill, New York N.Y., pp. 191-196.)

[0174] In mammalian cells, a number of viral-based expression systemsmay be utilized. In cases where an adenovirus is used as an expressionvector, sequences encoding GCREC may be ligated into an adenovirustranscription/translation complex consisting of the late promoter andtripartite leader sequence. Insertion in a non-essential E1 or E3 regionof the viral genome may be used to obtain infective virus whichexpresses GCREC in host cells. (See, e.g., Logan, J. and T. Shenk (1984)Proc. Natl. Acad. Sci. USA 81:3655-3659.) In addition, transcriptionenhancers, such as the Rous sarcoma virus (RSV) enhancer, may be used toincrease expression in mammalian host cells. SV40 or EBV-based vectorsmay also be used for high-level protein expression.

[0175] Human artificial chromosomes (HACs) may also be employed todeliver larger fragments of DNA than can be contained in and expressedfrom a plasmid. HACs of about 6 kb to 10 Mb are constructed anddelivered via conventional delivery methods (liposomes, polycationicamino polymers, or vesicles) for therapeutic purposes. (See, e.g.,Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355.)

[0176] For long term production of recombinant proteins in mammaliansystems, stable expression of GCREC in cell lines is preferred. Forexample, sequences encoding GCREC can be transformed into cell linesusing expression vectors which may contain viral origins of replicationand/or endogenous expression elements and a selectable marker gene onthe same or on a separate vector. Following the introduction of thevector, cells may be allowed to grow for about 1 to 2 days in enrichedmedia before being switched to selective media. The purpose of theselectable marker is to confer resistance to a selective agent, and itspresence allows growth and recovery of cells which successfully expressthe introduced sequences. Resistant clones of stably transformed cellsmay be propagated using tissue culture techniques appropriate to thecell type.

[0177] Any number of selection systems may be used to recovertransformed cell lines. These include, but are not limited to, theherpes simplex virus thymidine kinase and adeninephosphoribosyltransferase genes, for use in tk⁻ and apr⁻ cells,respectively. (See, e.g., Wigler, M. et al. (1977) Cell 11:223-232;Lowy, I. et al. (1980) Cell 22:817-823.) Also, antimetabolite,antibiotic, or herbicide resistance can be used as the basis forselection. For example, dhfr confers resistance to methotrexate; neoconfers resistance to the aminoglycosides neomycin and G418; and als andpat confer resistance to chlorsulfuron and phosphinotricinacetyltransferase, respectively. (See, e.g., Wigler, M. et al. (1980)Proc. Natl. Acad. Sci. USA 77:3567-3570; Colbere-Garapin, F. et al.(1981) J. Mol. Biol. 150:1-14.) Additional selectable genes have beendescribed, e.g., trpB and hisD, which alter cellular requirements formetabolites. (See, e.g., Hartman, S. C. and R. C. Mulligan (1988) Proc.Natl. Acad. Sci. USA 85:8047-8051.) Visible markers, e.g., anthocyanins,green fluorescent proteins (GFP; Clontech), β glucuronidase and itssubstrate β-glucuronide, or luciferase and its substrate luciferin maybe used. These markers can be used not only to identify transformants,but also to quantify the amount of transient or stable proteinexpression attributable to a specific vector system. (See, e.g., Rhodes,C. A. (1995) Methods Mol. Biol. 55:121-131.)

[0178] Although the presence/absence of marker gene expression suggeststhat the gene of interest is also present, the presence and expressionof the gene may need to be confirmed. For example, if the sequenceencoding GCREC is inserted within a marker gene sequence, transformedcells containing sequences encoding GCREC can be identified by theabsence of marker gene function. Alternatively, a marker gene can beplaced in tandem with a sequence encoding GCREC under the control of asingle promoter. Expression of the marker gene in response to inductionor selection usually indicates expression of the tandem gene as well.

[0179] In general, host cells that contain the nucleic acid sequenceencoding GCREC and that express GCREC may be identified by a variety ofprocedures known to those of skill in the art. These procedures include,but are not limited to, DNA-DNA or DNA-RNA hybridizations, PCRamplification, and protein bioassay or immunoassay techniques whichinclude membrane, solution, or chip based technologies for the detectionand/or quantification of nucleic acid or protein sequences.

[0180] Immunological methods for detecting and measuring the expressionof GCREC using either specific polyclonal or monoclonal antibodies areknown in the art. Examples of such techniques include enzyme-linkedimmunosorbent assays (ELISAs), radioimmunoassays (RIAs), andfluorescence activated cell sorting (FACS). A two-site, monoclonal-basedimmunoassay utilizing monoclonal antibodies reactive to twonon-interfering epitopes on GCREC is preferred, but a competitivebinding assay may be employed. These and other assays are well known inthe art. (See, e.g., Hampton, R. et al. (1990) Serological Methods, aLaboratory Manual, APS Press, St. Paul Minn., Sect. IV; Coligan, J. E.et al. (1997) Current Protocols in Immunology, Greene Pub. Associatesand Wiley-Interscience, New York N.Y.; and Pound, J. D. (1998)Immunochemical Protocols, Humana Press, Totowa N.J.)

[0181] A wide variety of labels and conjugation techniques are known bythose skilled in the art and may be used in various nucleic acid andamino acid assays. Means for producing labeled hybridization or PCRprobes for detecting sequences related to polynucleotides encoding GCRECinclude oligolabeling, nick translation, end-labeling, or PCRamplification using a labeled nucleotide. Alternatively, the sequencesencoding GCREC, or any fragments thereof, may be cloned into a vectorfor the production of an mRNA probe. Such vectors are known in the art,are commercially available, and may be used to synthesize RNA probes invitro by addition of an appropriate RNA polymerase such as T7, T3, orSP6 and labeled nucleotides. These procedures may be conducted using avariety of commercially available kits, such as those provided byAmersham Pharmacia Biotech, Promega (Madison Wis.), and US Biochemical.Suitable reporter molecules or labels which may be used for ease ofdetection include radionuclides, enzymes, fluorescent, chemiluminescent,or chromogenic agents, as well as substrates, cofactors, inhibitors,magnetic particles, and the like.

[0182] Host cells transformed with nucleotide sequences encoding GCRECmay be cultured under conditions suitable for the expression andrecovery of the protein from cell culture. The protein produced by atransformed cell may be secreted or retained intracellularly dependingon the sequence and/or the vector used. As will be understood by thoseof skill in the art, expression vectors containing polynucleotides whichencode GCREC may be designed to contain signal sequences which directsecretion of GCREC through a prokaryotic or eukaryotic cell membrane.

[0183] In addition, a host cell strain may be chosen for its ability tomodulate expression of the inserted sequences or to process theexpressed protein in the desired fashion. Such modifications of thepolypeptide include, but are not limited to, acetylation, carboxylation,glycosylation, phosphorylation, lipidation, and acylation.Post-translational processing which cleaves a “prepro” or “pro” form ofthe protein may also be used to specify protein targeting, folding,and/or activity. Different host cells which have specific cellularmachinery and characteristic mechanisms for post-translationalactivities (e.g., CHO, HeLa, MDCK, HEK293, and WI38) are available fromthe American Type Culture Collection (ATCC, Manassas Va.) and may bechosen to ensure the correct modification and processing of the foreignprotein.

[0184] In another embodiment of the invention, natural, modified, orrecombinant nucleic acid sequences encoding GCREC may be ligated to aheterologous sequence resulting in translation of a fusion protein inany of the aforementioned host systems. For example, a chimeric GCRECprotein containing a heterologous moiety that can be recognized by acommercially available antibody may facilitate the screening of peptidelibraries for inhibitors of GCREC activity. Heterologous protein andpeptide moieties may also facilitate purification of fusion proteinsusing commercially available affinity matrices. Such moieties include,but are not limited to, glutathione S-transferase (GST), maltose bindingprotein (MBP), thioredoxin (Trx), calmodulin binding peptide (CBP),6-His, FLAG, c-myc, and hemagglutinin (HA). GST, MBP, Trx, CBP, and6-His enable purification of their cognate fusion proteins onimmobilized glutathione, maltose, phenylarsine oxide, calmodulin, andmetal-chelate resins, respectively. FLAG, c-myc, and hemagglutinin (HA)enable immunoaffinity purification of fusion proteins using commerciallyavailable monoclonal and polyclonal antibodies that specificallyrecognize these epitope tags. A fusion protein may also be engineered tocontain a proteolytic cleavage site located between the GCREC encodingsequence and the heterologous protein sequence, so that GCREC may becleaved away from the heterologous moiety following purification.Methods for fusion protein expression and purification are discussed inAusubel (1995, supra, ch. 10). A variety of commercially available kitsmay also be used to facilitate expression and purification of fusionproteins.

[0185] In a further embodiment of the invention, synthesis ofradiolabeled GCREC may be achieved in vitro using the TNT rabbitreticulocyte lysate or wheat germ extract system (Promega). Thesesystems couple transcription and translation of protein-coding sequencesoperably associated with the T7, T3, or SP6 promoters. Translation takesplace in the presence of a radiolabeled amino acid precursor, forexample, ³⁵S-methionine.

[0186] GCREC of the present invention or fragments thereof may be usedto screen for compounds that specifically bind to GCREC. At least oneand up to a plurality of test compounds may be screened for specificbinding to GCREC. Examples of test compounds include antibodies,oligonucleotides, proteins (e.g., receptors), or small molecules.

[0187] In one embodiment, the compound thus identified is closelyrelated to the natural ligand of GCREC, e.g., a ligand or fragmentthereof, a natural substrate, a structural or functional mimetic, or anatural binding partner. (See, e.g., Coligan, J. E. et al. (1991)Current Protocols in Immunology 1(2): Chapter 5.) Similarly, thecompound can be closely related to the natural receptor to which GCRECbinds, or to at least a fragment of the receptor, e.g., the ligandbinding site. In either case, the compound can be rationally designedusing known techniques. In one embodiment, screening for these compoundsinvolves producing appropriate cells which express GCREC, either as asecreted protein or on the cell membrane. Preferred cells include cellsfrom mammals, yeast, Drosophila, or E. coli. Cells expressing GCREC orcell membrane fractions which contain GCREC are then contacted with atest compound and binding, stimulation, or inhibition of activity ofeither GCREC or the compound is analyzed.

[0188] An assay may simply test binding of a test compound to thepolypeptide, wherein binding is detected by a fluorophore, radioisotope,enzyme conjugate, or other detectable label. For example, the assay maycomprise the steps of combining at least one test compound with GCREC,either in solution or affixed to a solid support, and detecting thebinding of GCREC to the compound. Alternatively, the assay may detect ormeasure binding of a test compound in the presence of a labeledcompetitor. Additionally, the assay may be carried out using cell-freepreparations, chemical libraries, or natural product mixtures, and thetest compound(s) may be free in solution or affixed to a solid support.

[0189] GCREC of the present invention or fragments thereof may be usedto screen for compounds that modulate the activity of GCREC. Suchcompounds may include agonists, antagonists, or partial or inverseagonists. In one embodiment, an assay is preformed under conditionspermissive for GCREC activity, wherein GCREC is combined with at leastone test compound, and the activity of GCREC in the presence of a testcompound is compared with the activity of GCREC in the absence of thetest compound. A change in the activity of GCREC in the presence of thetest compound is indicative of a compound that modulates the activity ofGCREC. Alternatively, a test compound is combined with an in vitro orcell-free system comprising GCREC under conditions suitable for GCRECactivity, and the assay is performed. In either of these assays, a testcompound which modulates the activity of GCREC may do so indirectly andneed not come in direct contact with the test compound. At least one andup to a plurality of test compounds may be screened.

[0190] In another embodiment, polynucleotides encoding GCREC or theirmammalian homologs may be “knocked out” in an animal model system usinghomologous recombination in embryonic stem (ES) cells. Such techniquesare well known in the art and are useful for the generation of animalmodels of human disease. (See, e.g., U.S. Pat. No. 5,175,383 and U.S.Pat. No. 5,767,337.) For example, mouse ES cells, such as the mouse129/SvJ cell line, are derived from the early mouse embryo and grown inculture. The ES cells are transformed with a vector containing the geneof interest disrupted by a marker gene, e.g., the neomycinphosphotransferase gene (neo; Capecchi, M. R. (1989) Science244:1288-1292). The vector integrates into the corresponding region ofthe host genome by homologous recombination. Alternatively, homologousrecombination takes place using the Cre-loxP system to knockout a geneof interest in a tissue- or developmental stage-specific manner (Marth,J. D. (1996) Clin. Invest. 97:1999-2002; Wagner, K. U. et al. (1997)Nucleic Acids Res. 25:4323-4330). Transformed ES cells are identifiedand microinjected into mouse cell blastocysts such as those from theC57BL/6 mouse strain. The blastocysts are surgically transferred topseudopregnant dams, and the resulting chimeric progeny are genotypedand bred to produce heterozygous or homozygous strains. Transgenicanimals thus generated may be tested with potential therapeutic or toxicagents.

[0191] Polynucleotides encoding GCREC may also be manipulated in vitroin ES cells derived from human blastocysts. Human ES cells have thepotential to differentiate into at least eight separate cell lineagesincluding endoderm, mesoderm, and ectodermal cell types. These celllineages differentiate into, for example, neural cells, hematopoieticlineages, and cardiomyocytes (Thomson, J. A. et al. (1998) Science282:1145-1147).

[0192] Polynucleotides encoding GCREC can also be used to create“knockin” humanized animals (pigs) or transgenic animals (mice or rats)to model human disease. With knockin technology, a region of apolynucleotide encoding GCREC is injected into animal ES cells, and theinjected sequence integrates into the animal cell genome. Transformedcells are injected into blastulae, and the blastulae are implanted asdescribed above. Transgenic progeny or inbred lines are studied andtreated with potential pharmaceutical agents to obtain information ontreatment of a human disease. Alternatively, a mammal inbred tooverexpress GCREC, e.g., by secreting GCREC in its milk, may also serveas a convenient source of that protein (Janne, J. et al. (1998)Biotechnol. Annu. Rev. 4:55-74).

[0193] Therapeutics

[0194] Chemical and structural similarity, e.g., in the context ofsequences and motifs, exists between regions of GCREC and G-proteincoupled receptors. In addition, examples of tissues expressing GCREC areperipheral blood cells, and human mammary epithelial cells, and also canbe found in Table 6. Therefore, GCREC appears to play a role in cellproliferative, neurological, cardiovascular, gastrointestinal,autoimmune/inflammatory, and metabolic disorders, and viral infections.In the treatment of disorders associated with increased GCREC expressionor activity, it is desirable to decrease the expression or activity ofGCREC. In the treatment of disorders associated with decreased GCRECexpression or activity, it is desirable to increase the expression oractivity of GCREC.

[0195] Therefore, in one embodiment, GCREC or a fragment or derivativethereof may be administered to a subject to treat or prevent a disorderassociated with decreased expression or activity of GCREC. Examples ofsuch disorders include, but are not limited to, a cell proliferativedisorder such as actinic keratosis, arteriosclerosis, atherosclerosis,bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD),myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera,psoriasis, primary thrombocythemia, and cancers includingadenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma,teratocarcinoma, and, in particular, cancers of the adrenal gland,bladder, bone, bone marrow, brain, breast, cervix, gall bladder,ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle,ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin,spleen, testis, thymus, thyroid, and uterus; a neurological disordersuch as epilepsy, ischemic cerebrovascular disease, stroke, cerebralneoplasms, Alzheimer's disease, Pick's disease, Huntington's disease,dementia, Parkinson's disease and other extrapyramidal disorders,amyotrophic lateral sclerosis and other motor neuron disorders,progressive neural muscular atrophy, retinitis pigmentosa, hereditaryataxias, multiple sclerosis and other demyelinating diseases, bacterialand viral meningitis, brain abscess, subdural empyema, epidural abscess,suppurative intracranial thrombophlebitis, myelitis and radiculitis,viral central nervous system disease, prion diseases including kuru,Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome,fatal familial insomnia, nutritional and metabolic diseases of thenervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinalhemangioblastomatosis, encephalotrigeminal syndrome, mental retardationand other developmental disorders of the central nervous system,cerebral palsy, neuroskeletal disorders, autonomic nervous systemdisorders, cranial nerve disorders, spinal cord diseases, musculardystrophy and other neuromuscular disorders, peripheral nervous systemdisorders, dermatomyositis and polymyositis, inherited, metabolic,endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis,mental disorders including mood, anxiety, and schizophrenic disorders,seasonal affective disorder (SAD), akathesia, amnesia, catatonia,diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses,postherpetic neuralgia, Tourette's disorder, progressive supranuclearpalsy, corticobasal degeneration, and familial frontotemporal dementia;a cardiovascular disorder such as arteriovenous fistula,atherosclerosis, hypertension, vasculitis, Raynaud's disease, aneurysms,arterial dissections, varicose veins, thrombophlebitis andphlebothrombosis, vascular tumors, complications of thrombolysis,balloon angioplasty, vascular replacement, and coronary artery bypassgraft surgery, congestive heart failure, ischemic heart disease, anginapectoris, myocardial infarction, hypertensive heart disease,degenerative valvular heart disease, calcific aortic valve stenosis,congenitally bicuspid aortic valve, mitral annular calcification, mitralvalve prolapse, rheumatic fever and rheumatic heart disease, infectiveendocarditis, nonbacterial thrombotic endocarditis, endocarditis ofsystemic lupus erythematosus, carcinoid heart disease, cardiomyopathy,myocarditis, pericarditis, neoplastic heart disease, congenital heartdisease, and complications of cardiac transplantation; agastrointestinal disorder such as dysphagia, peptic esophagitis,esophageal spasm, esophageal stricture, esophageal carcinoma, dyspepsia,indigestion, gastritis, gastric carcinoma, anorexia, nausea, emesis,gastroparesis, antral or pyloric edema, abdominal angina, pyrosis,gastroenteritis, intestinal obstruction, infections of the intestinaltract, peptic ulcer, cholelithiasis, cholecystitis, cholestasis,pancreatitis, pancreatic carcinoma, biliary tract disease, hepatitis,hyperbilirubinemia, cirrhosis, passive congestion of the liver,hepatoma, infectious colitis, ulcerative colitis, ulcerative proctitis,Crohn's disease, Whipple's disease, Mallory-Weiss syndrome, coloniccarcinoma, colonic obstruction, irritable bowel syndrome, short bowelsyndrome, diarrhea, constipation, gastrointestinal hemorrhage, acquiredimmunodeficiency syndrome (AIDS) enteropathy, jaundice, hepaticencephalopathy, hepatorenal syndrome, hepatic steatosis,hemochromatosis, Wilson's disease, alpha₁-antitrypsin deficiency, Reye'ssyndrome, primary sclerosing cholangitis, liver infarction, portal veinobstruction and thrombosis, centrilobular necrosis, peliosis hepatis,hepatic vein thrombosis, veno-occlusive disease, preeclampsia,eclampsia, acute fatty liver of pregnancy, intrahepatic cholestasis ofpregnancy, and hepatic tumors including nodular hyperplasias, adenomas,and carcinomas; an autoimmune/inflammatory disorder such as acquiredimmunodeficiency syndrome (AIDS), Addison's disease, adult respiratorydistress syndrome, allergies, ankylosing spondylitis, amyloidosis,anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmunethyroiditis, autoimmune polyendocrinopathy-candidiasis-ectodermaldystrophy (APECED), bronchitis, cholecystitis, contact dermatitis,Crohn's disease, atopic dermatitis, dermatomyositis, diabetes mellitus,emphysema, episodic lymphopenia with lymphocytotoxins, erythroblastosisfetalis, erythema nodosum, atrophic gastritis, glomerulonephritis,Goodpasture's syndrome, gout, Graves' disease, Hashimoto's thyroiditis,hypereosinophilia, irritable bowel syndrome, multiple sclerosis,myasthenia gravis, myocardial or pericardial inflammation,osteoarthritis, osteoporosis, pancreatitis, polymyositis, psoriasis,Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjögren'ssyndrome, systemic anaphylaxis, systemic lupus erythematosus, systemicsclerosis, thrombocytopenic purpura, ulcerative colitis, uveitis, Wernersyndrome, complications of cancer, hemodialysis, and extracorporealcirculation, viral, bacterial, fungal, parasitic, protozoal, andhelminthic infections, and trauma; a metabolic disorder such asdiabetes, obesity, and osteoporosis; and an infection by a viral agentclassified as adenovirus, arenavirus, bunyavirus, calicivirus,coronavirus, filovirus, hepadnavirus, herpesvirus, flavivirus,orthomyxovirus, parvovirus, papovavirus, paramyxovirus, picornavirus,poxvirus, reovirus, retrovirus, rhabdovirus, and tongavirus.

[0196] In another embodiment, a vector capable of expressing GCREC or afragment or derivative thereof may be administered to a subject to treator prevent a disorder associated with decreased expression or activityof GCREC including, but not limited to, those described above.

[0197] In a further embodiment, a composition comprising a substantiallypurified GCREC in conjunction with a suitable pharmaceutical carrier maybe administered to a subject to treat or prevent a disorder associatedwith decreased expression or activity of GCREC including, but notlimited to, those provided above.

[0198] In still another embodiment, an agonist which modulates theactivity of GCREC may be administered to a subject to treat or prevent adisorder associated with decreased expression or activity of GCRECincluding, but not limited to, those listed above.

[0199] In a further embodiment, an antagonist of GCREC may beadministered to a subject to treat or prevent a disorder associated withincreased expression or activity of GCREC. Examples of such disordersinclude, but are not limited to, those cell proliferative, neurological,cardiovascular, gastrointestinal, autoimmune/inflammatory, and metabolicdisorders, and viral infections described above. In one aspect, anantibody which specifically binds GCREC may be used directly as anantagonist or indirectly as a targeting or delivery mechanism forbringing a pharmaceutical agent to cells or tissues which express GCREC.

[0200] In an additional embodiment, a vector expressing the complementof the polynucleotide encoding GCREC may be administered to a subject totreat or prevent a disorder associated with increased expression oractivity of GCREC including, but not limited to, those described above.

[0201] In other embodiments, any of the proteins, antagonists,antibodies, agonists, complementary sequences, or vectors of theinvention may be administered in combination with other appropriatetherapeutic agents. Selection of the appropriate agents for use incombination therapy may be made by one of ordinary skill in the art,according to conventional pharmaceutical principles. The combination oftherapeutic agents may act synergistically to effect the treatment orprevention of the various disorders described above. Using thisapproach, one may be able to achieve therapeutic efficacy with lowerdosages of each agent, thus reducing the potential for adverse sideeffects.

[0202] An antagonist of GCREC may be produced using methods which aregenerally known in the art. In particular, purified GCREC may be used toproduce antibodies or to screen libraries of pharmaceutical agents toidentify those which specifically bind GCREC. Antibodies to GCREC mayalso be generated using methods that are well known in the art. Suchantibodies may include, but are not limited to, polyclonal, monoclonal,chimeric, and single chain antibodies, Fab fragments, and fragmentsproduced by a Fab expression library. Neutralizing antibodies (i.e.,those which inhibit dimer formation) are generally preferred fortherapeutic use. Single chain antibodies (e.g., from camels or llamas)may be potent enzyme inhibitors and may have advantages in the design ofpeptide mimetics, and in the development of immuno-adsorbents andbiosensors (Muyldermans, S. (2001) J. Biotechnol. 74:277-302).

[0203] For the production of antibodies, various hosts including goats,rabbits, rats, mice, camels, dromedaries, llamas, humans, and others maybe immunized by injection with GCREC or with any fragment oroligopeptide thereof which has immunogenic properties. Depending on thehost species, various adjuvants may be used to increase immunologicalresponse. Such adjuvants include, but are not limited to, Freund's,mineral gels such as aluminum hydroxide, and surface active substancessuch as lysolecithin, pluronic polyols, polyanions, peptides, oilemulsions, KLH, and dinitrophenol. Among adjuvants used in humans, BCG(bacilli Calmette-Guerin) and Corynebacterium parvum are especiallypreferable.

[0204] It is preferred that the oligopeptides, peptides, or fragmentsused to induce antibodies to GCREC have an amino acid sequenceconsisting of at least about 5 amino acids, and generally will consistof at least about 10 amino acids. It is also preferable that theseoligopeptides, peptides, or fragments are identical to a portion of theamino acid sequence of the natural protein. Short stretches of GCRECamino acids may be fused with those of another protein, such as KLH, andantibodies to the chimeric molecule may be produced.

[0205] Monoclonal antibodies to GCREC may be prepared using anytechnique which provides for the production of antibody molecules bycontinuous cell lines in culture. These include, but are not limited to,the hybridoma technique, the human B-cell hybridoma technique, and theEBV-hybridoma technique. (See, e.g., Kohler, G. et al. (1975) Nature256:495-497; Kozbor, D. et al. (1985) J. Immunol. Methods 81:31-42;Cote, R. J. et al. (1983) Proc. Natl. Acad. Sci. USA 80:2026-2030; andCole, S. P. et al. (1984) Mol. Cell Biol. 62:109-120.)

[0206] In addition, techniques developed for the production of “chimericantibodies,” such as the splicing of mouse antibody genes to humanantibody genes to obtain a molecule with appropriate antigen specificityand biological activity, can be used. (See, e.g., Morrison, S. L. et al.(1984) Proc. Natl. Acad. Sci. USA 81:6851-6855; Neuberger, M. S. et al.(1984) Nature 312:604-608; and Takeda, S. et al. (1985) Nature314:452-454.) Alternatively, techniques described for the production ofsingle chain antibodies may be adapted, using methods known in the art,to produce GCREC-specific single chain antibodies. Antibodies withrelated specificity, but of distinct idiotypic composition, may begenerated by chain shuffling from random combinatorial immunoglobulinlibraries. (See, e.g., Burton, D. R. (1991) Proc. Natl. Acad. Sci. USA88:10134-10137.)

[0207] Antibodies may also be produced by inducing in vivo production inthe lymphocyte population or by screening immunoglobulin libraries orpanels of highly specific binding reagents as disclosed in theliterature. (See, e.g., Orlandi, R. et al. (1989) Proc. Natl. Acad. Sci.USA 86:3833-3837; Winter, G. et al. (1991) Nature 349:293-299.)

[0208] Antibody fragments which contain specific binding sites for GCRECmay also be generated. For example, such fragments include, but are notlimited to, F(ab′)₂ fragments produced by pepsin digestion of theantibody molecule and Fab fragments generated by reducing the disulfidebridges of the F(ab′)2 fragments. Alternatively, Fab expressionlibraries may be constructed to allow rapid and easy identification ofmonoclonal Fab fragments with the desired specificity. (See, e.g., Huse,W. D. et al. (1989) Science 246:1275-1281.)

[0209] Various immunoassays may be used for screening to identifyantibodies having the desired specificity. Numerous protocols forcompetitive binding or immunoradiometric assays using either polyclonalor monoclonal antibodies with established specificities are well knownin the art. Such immunoassays typically involve the measurement ofcomplex formation between GCREC and its specific antibody. A two-site,monoclonal-based immunoassay utilizing monoclonal antibodies reactive totwo non-interfering GCREC epitopes is generally used, but a competitivebinding assay may also be employed (Pound, supra).

[0210] Various methods such as Scatchard analysis in conjunction withradioimmunoassay techniques may be used to assess the affinity ofantibodies for GCREC. Affinity is expressed as an association constant,K_(a), which is defined as the molar concentration of GCREC-antibodycomplex divided by the molar concentrations of free antigen and freeantibody under equilibrium conditions. The K_(a) determined for apreparation of polyclonal antibodies, which are heterogeneous in theiraffinities for multiple GCREC epitopes, represents the average affinity,or avidity, of the antibodies for GCREC. The K_(a) determined for apreparation of monoclonal antibodies, which are monospecific for aparticular GCREC epitope, represents a true measure of affinity.High-affinity antibody preparations with K_(a) ranging from about 10⁹ to10¹² L/mole are preferred for use in immunoassays in which theGCREC-antibody complex must withstand rigorous manipulations.Low-affinity antibody preparations with K_(a) ranging from about 10⁶ to10⁷ L/mole are preferred for use in immunopurification and similarprocedures which ultimately require dissociation of GCREC, preferably inactive form, from the antibody (Catty, D. (1988) Antibodies, Volume I: APractical Approach, IRL Press, Washington DC; Liddell, J. E. and A.Cryer (1991) A Practical Guide to Monoclonal Antibodies, John Wiley &Sons, New York N.Y.).

[0211] The titer and avidity of polyclonal antibody preparations may befurther evaluated to determine the quality and suitability of suchpreparations for certain downstream applications. For example, apolyclonal antibody preparation containing at least 1-2 mg specificantibody/ml, preferably 5-10 mg specific antibody/ml, is generallyemployed in procedures requiring precipitation of GCREC-antibodycomplexes. Procedures for evaluating antibody specificity, titer, andavidity, and guidelines for antibody quality and usage in variousapplications, are generally available. (See, e.g., Catty, supra, andColigan et al. supra.)

[0212] In another embodiment of the invention, the polynucleotidesencoding GCREC, or any fragment or complement thereof, may be used fortherapeutic purposes. In one aspect, modifications of gene expressioncan be achieved by designing complementary sequences or antisensemolecules (DNA, RNA, PNA, or modified oligonucleotides) to the coding orregulatory regions of the gene encoding GCREC. Such technology is wellknown in the art, and antisense oligonucleotides or larger fragments canbe designed from various locations along the coding or control regionsof sequences encoding GCREC. (See, e.g., Agrawal, S., ed. (1996)Antisense Therapeutics, Humana Press Inc., Totawa N.J.)

[0213] In therapeutic use, any gene delivery system suitable forintroduction of the antisense sequences into appropriate target cellscan be used. Antisense sequences can be delivered intracellularly in theform of an expression plasmid which, upon transcription, produces asequence complementary to at least a portion of the cellular sequenceencoding the target protein. (See, e.g., Slater, J. E. et al. (1998) J.Allergy Clin. Immunol. 102(3):469-475; and Scanlon, K. J. et al. (1995)9(13):1288-1296.) Antisense sequences can also be introducedintracellularly through the use of viral vectors, such as retrovirus andadeno-associated virus vectors. (See, e.g., Miller, A. D. (1990) Blood76:271; Ausubel, supra; Uckert, W. and W. Walther (1994) Pharmacol.Ther. 63(3):323-347.) Other gene delivery mechanisms includeliposome-derived systems, artificial viral envelopes, and other systemsknown in the art. (See, e.g., Rossi, J. J. (1995) Br. Med. Bull.51(1):217-225; Boado, R. J. et al. (1998) J. Pharm. Sci.87(11):1308-1315; and Morris, M. C. et al. (1997) Nucleic Acids Res.25(14):2730-2736.)

[0214] In another embodiment of the invention, polynucleotides encodingGCREC may be used for somatic or germline gene therapy. Gene therapy maybe performed to (i) correct a genetic deficiency (e.g., in the cases ofsevere combined immunodeficiency (SCID)-X1 disease characterized byX-linked inheritance (Cavazzana-Calvo, M. et al. (2000) Science288:669-672), severe combined immunodeficiency syndrome associated withan inherited adenosine deaminase (ADA) deficiency (Blaese, R. M. et al.(1995) Science 270:475-480; Bordignon, C. et al. (1995) Science270:470-475), cystic fibrosis (Zabner, J. et al. (1993) Cell 75:207-216;Crystal, R. G. et al. (1995) Hum. Gene Therapy 6:643-666; Crystal, R. G.et al. (1995) Hum. Gene Therapy 6:667-703), thalassamias, familialhypercholesterolemia, and hemophilia resulting from Factor VIII orFactor IX deficiencies (Crystal, R. G. (1995) Science 270:404-410;Verma, I. M. and N. Somia (1997) Nature 389:239-242)), (ii) express aconditionally lethal gene product (e.g., in the case of cancers whichresult from unregulated cell proliferation), or (iii) express a proteinwhich affords protection against intracellular parasites (e.g., againsthuman retroviruses, such as human immunodeficiency virus (HIV)(Baltimore, D. (1988) Nature 335:395-396; Poeschla, E. et al. (1996)Proc. Natl. Acad. Sci. USA 93:11395-11399), hepatitis B or C virus (HBV,HCV); fungal parasites, such as Candida albicans and Paracoccidioidesbrasiliensis; and protozoan parasites such as Plasmodium falciparum andTrypanosoma cruzi). In the case where a genetic deficiency in GCRECexpression or regulation causes disease, the expression of GCREC from anappropriate population of transduced cells may alleviate the clinicalmanifestations caused by the genetic deficiency.

[0215] In a further embodiment of the invention, diseases or disorderscaused by deficiencies in OCREC are treated by constructing mammalianexpression vectors encoding GCREC and introducing these vectors bymechanical means into GCREC-deficient cells. Mechanical transfertechnologies for use with cells in vivo or ex vitro include (i) directDNA microinjection into individual cells, (ii) ballistic gold particledelivery, (iii) liposome-mediated transfection, (iv) receptor-mediatedgene transfer, and (v) the use of DNA transposons (Morgan, R. A. and W.F. Anderson (1993) Annu. Rev. Biochem. 62:191-217; Ivics, Z. (1997) Cell91:501-510; Boulay, J -L. and H. Récipon (1998) Curr. Opin. Biotechnol.9:445-450).

[0216] Expression vectors that may be effective for the expression ofGCREC include, but are not limited to, the PCDNA 3.1, EPITAG, PRCCMV2,PREP, PVAX, PCR2-TOPOTA vectors (Invitrogen, Carlsbad Calif.),PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Stratagene, La Jolla Calif.), andPTET-OFF, PTET-ON, PTRE2, PTRE2-LUC, PTK-HYG (Clontech, Palo AltoCalif.). GCREC may be expressed using (i) a constitutively activepromoter, (e.g., from cytomegalovirus (CMV), Rous sarcoma virus (RSV),SV40 virus, thymidine kinase (TK), or β-actin genes), (ii) an induciblepromoter (e.g., the tetracycline-regulated promoter (Gossen, M. and H.Bujard (1992) Proc. Natl. Acad. Sci. USA 89:5547-5551; Gossen, M. et al.(1995) Science 268:1766-1769; Rossi, F. M. V. and H. M. Blau (1998)Curr. Opin. Biotechnol. 9:451-456), commercially available in the T-REXplasmid (Invitrogen)); the ecdysone-inducible promoter (available in theplasmids PVGRXR and PIND; Invitrogen); the FK506/rapamycin induciblepromoter; or the RU486/mifepristone inducible promoter (Rossi, F. M. V.and H. M. Blau, supra)), or (iii) a tissue-specific promoter or thenative promoter of the endogenous gene encoding GCREC from a normalindividual.

[0217] Commercially available liposome transformation kits (e.g., thePERFECT LIPID TRANSFECTION KIT, available from Invitrogen) allow onewith ordinary skill in the art to deliver polynucleotides to targetcells in culture and require minimal effort to optimize experimentalparameters. In the alternative, transformation is performed using thecalcium phosphate method (Graham, F. L. and A. J. Eb (1973) Virology52:456-467), or by electroporation (Neumann, E. et al. (1982) EMBO J.1:841-845). The introduction of DNA to primary cells requiresmodification of these standardized mammalian transfection protocols.

[0218] In another embodiment of the invention, diseases or disorderscaused by genetic defects with respect to GCREC expression are treatedby constructing a retrovirus vector consisting of (i) the polynucleotideencoding GCREC under the control of an independent promoter or theretrovirus long terminal repeat (LTR) promoter, (ii) appropriate RNApackaging signals, and (iii) a Rev-responsive element (RRE) along withadditional retrovirus cis-acting RNA sequences and coding sequencesrequired for efficient vector propagation. Retrovirus vectors (e.g., PFBand PFBNEO) are commercially available (Stratagene) and are based onpublished data (Riviere, I. et al. (1995) Proc. Natl. Acad. Sci. USA92:6733-6737), incorporated by reference herein. The vector ispropagated in an appropriate vector producing cell line (VPCL) thatexpresses an envelope gene with a tropism for receptors on the targetcells or a promiscuous envelope protein such as VSVg (Armentano, D. etal. (1987) J. Virol. 61:1647-1650; Bender, M. A. et al. (1987) J. Virol.61:1639-1646; Adam, M. A. and A. D. Miller (1988) J. Virol.62:3802-3806; Dull, T. et al. (1998) J. Virol. 72:8463-8471; Zufferey,R. et al. (1998) J. Virol. 72:9873-9880). U.S. Pat. No. 5,910,434 toRigg (“Method for obtaining retrovirus packaging cell lines producinghigh transducing efficiency retroviral supernatant”) discloses a methodfor obtaining retrovirus packaging cell lines and is hereby incorporatedby reference. Propagation of retrovirus vectors, transduction of apopulation of cells (e.g., CD4+ T-cells), and the return of transducedcells to a patient are procedures well known to persons skilled in theart of gene therapy and have been well documented (Ranga, U. et al.(1997) J. Virol. 71:7020-7029; Bauer, G. et al. (1997) Blood89:2259-2267; Bonyhadi, M. L. (1997) J. Virol. 71:4707-4716; Ranga, U.et al. (1998) Proc. Natl. Acad. Sci. USA 95:1201-1206; Su, L. (1997)Blood 89:2283-2290).

[0219] In the alternative, an adenovirus-based gene therapy deliverysystem is used to deliver polynucleotides encoding GCREC to cells whichhave one or more genetic abnormalities with respect to the expression ofGCREC. The construction and packaging of adenovirus-based vectors arewell known to those with ordinary skill in the art. Replicationdefective adenovirus vectors have proven to be versatile for importinggenes encoding immunoregulatory proteins into intact islets in thepancreas (Csete, M. E. et al. (1995) Transplantation 27:263-268).Potentially useful adenoviral vectors are described in U.S. Pat. No.5,707,618 to Armentano (“Adenovirus vectors for gene therapy”), herebyincorporated by reference. For adenoviral vectors, see also Antinozzi,P. A. et al. (1999) Annu. Rev. Nutr. 19:511-544 and Verma, I. M. and N.Somia (1997) Nature 18:389:239-242, both incorporated by referenceherein.

[0220] In another alternative, a herpes-based, gene therapy deliverysystem is used to deliver polynucleotides encoding GCREC to target cellswhich have one or more genetic abnormalities with respect to theexpression of GCREC. The use of herpes simplex virus (HSV)-based vectorsmay be especially valuable for introducing GCREC to cells of the centralnervous system, for which HSV has a tropism. The construction andpackaging of herpes-based vectors are well known to those with ordinaryskill in the art. A replication-competent herpes simplex virus (HSV)type 1-based vector has been used to deliver a reporter gene to the eyesof primates (Liu, X. et al. (1999) Exp. Eye Res. 169:385-395). Theconstruction of a HSV-1 virus vector has also been disclosed in detailin U.S. Pat. No. 5,804,413 to DeLuca (“Herpes simplex virus strains forgene transfer”), which is hereby incorporated by reference. U.S. Pat.No. 5,804,413 teaches the use of recombinant HSV d92 which consists of agenome containing at least one exogenous gene to be transferred to acell under the control of the appropriate promoter for purposesincluding human gene therapy. Also taught by this patent are theconstruction and use of recombinant HSV strains deleted for ICP4, ICP27and ICP22. For HSV vectors, see also Goins, W. F. et al. (1999) J.Virol. 73:519-532 and Xu, H. et al. (1994) Dev. Biol. 163:152-161,hereby incorporated by reference. The manipulation of cloned herpesvirussequences, the generation of recombinant virus following thetransfection of multiple plasmids containing different segments of thelarge herpesvirus genomes, the growth and propagation of herpesvirus,and the infection of cells with herpesvirus are techniques well known tothose of ordinary skill in the art.

[0221] In another alternative, an alphavirus (positive, single-strandedRNA virus) vector is used to deliver polynucleotides encoding GCREC totarget cells. The biology of the prototypic alphavirus, Semliki ForestVirus (SFV), has been studied extensively and gene transfer vectors havebeen based on the SFV genome (Garoff, H. and K. -J. Li (1998) Curr.Opin. Biotechnol. 9:464-469). During alphavirus RNA replication, asubgenomic RNA is generated that normally encodes the viral capsidproteins. This subgenomic RNA replicates to higher levels than the fulllength genomic RNA, resulting in the overproduction of capsid proteinsrelative to the viral proteins with enzymatic activity (e.g., proteaseand polymerase). Similarly, inserting the coding sequence for GCREC intothe alphavirus genome in place of the capsid-coding region results inthe production of a large number of GCREC-coding RNAs and the synthesisof high levels of GCREC in vector transduced cells. While alphavirusinfection is typically associated with cell lysis within a few days, theability to establish a persistent infection in hamster normal kidneycells (BHK-21) with a variant of Sindbis virus (SIN) indicates that thelytic replication of alphaviruses can be altered to suit the needs ofthe gene therapy application (Dryga, S. A. et al. (1997) Virology228:74-83). The wide host range of alphaviruses will allow theintroduction of GCREC into a variety of cell types. The specifictransduction of a subset of cells in a population may require thesorting of cells prior to transduction. The methods of manipulatinginfectious cDNA clones of alphaviruses, performing alphavirus cDNA andRNA transfections, and performing alphavirus infections, are well knownto those with ordinary skill in the art.

[0222] Oligonucleotides derived from the transcription initiation site,e.g., between about positions −10 and +10 from the start site, may alsobe employed to inhibit gene expression. Similarly, inhibition can beachieved using triple helix base-pairing methodology. Triple helixpairing is useful because it causes inhibition of the ability of thedouble helix to open sufficiently for the binding of polymerases,transcription factors, or regulatory molecules. Recent therapeuticadvances using triplex DNA have been described in the literature. (See,e.g., Gee, J. E. et al. (1994) in Huber, B. E. and B. I. Carr, Molecularand Immunologic Approaches, Futura Publishing, Mt. Kisco N.Y., pp.163-177.) A complementary sequence or antisense molecule may also bedesigned to block translation of mRNA by preventing the transcript frombinding to ribosomes.

[0223] Ribozymes, enzymatic RNA molecules, may also be used to catalyzethe specific cleavage of RNA. The mechanism of ribozyme action involvessequence-specific hybridization of the ribozyme molecule tocomplementary target RNA, followed by endonucleolytic cleavage. Forexample, engineered hammerhead motif ribozyme molecules may specificallyand efficiently catalyze endonucleolytic cleavage of sequences encodingGCREC.

[0224] Specific ribozyme cleavage sites within any potential RNA targetare initially identified by scanning the target molecule for ribozymecleavage sites, including the following sequences: GUA, GUU, and GUC.Once identified, short RNA sequences of between 15 and 20ribonucleotides, corresponding to the region of the target genecontaining the cleavage site, may be evaluated for secondary structuralfeatures which may render the oligonucleotide inoperable. Thesuitability of candidate targets may also be evaluated by testingaccessibility to hybridization with complementary oligonucleotides usingribonuclease protection assays.

[0225] Complementary ribonucleic acid molecules and ribozymes of theinvention may be prepared by any method known in the art for thesynthesis of nucleic acid molecules. These include techniques forchemically synthesizing oligonucleotides such as solid phasephosphoramidite chemical synthesis. Alternatively, RNA molecules may begenerated by in vitro and in vivo transcription of DNA sequencesencoding GCREC. Such DNA sequences may be incorporated into a widevariety of vectors with suitable RNA polymerase promoters such as T7 orSP6. Alternatively, these cDNA constructs that synthesize complementaryRNA, constitutively or inducibly, can be introduced into cell lines,cells, or tissues.

[0226] RNA molecules may be modified to increase intracellular stabilityand half-life. Possible modifications include, but are not limited to,the addition of flanking sequences at the 5′ and/or 3′ ends of themolecule, or the use of phosphorothioate or 2′O-methyl rather thanphosphodiesterase linkages within the backbone of the molecule. Thisconcept is inherent in the production of PNAs and can be extended in allof these molecules by the inclusion of nontraditional bases such asinosine, queosine, and wybutosine, as well as acetyl-, methyl-, thio-,and similarly modified forms of adenine, cytidine, guanine, thymine, anduridine which are not as easily recognized by endogenous endonucleases.

[0227] An additional embodiment of the invention encompasses a methodfor screening for a compound which is effective in altering expressionof a polynucleotide encoding GCREC. Compounds which may be effective inaltering expression of a specific polynucleotide may include, but arenot limited to, oligonucleotides, antisense oligonucleotides, triplehelix-forming oligonucleotides, transcription factors and otherpolypeptide transcriptional regulators, and non-macromolecular chemicalentities which are capable of interacting with specific polynucleotidesequences. Effective compounds may alter polynucleotide expression byacting as either inhibitors or promoters of polynucleotide expression.Thus, in the treatment of disorders associated with increased GCRECexpression or activity, a compound which specifically inhibitsexpression of the polynucleotide encoding GCREC may be therapeuticallyuseful, and in the treatment of disorders associated with decreasedGCREC expression or activity, a compound which specifically promotesexpression of the polynucleotide encoding GCREC may be therapeuticallyuseful.

[0228] At least one, and up to a plurality, of test compounds may bescreened for effectiveness in altering expression of a specificpolynucleotide. A test compound may be obtained by any method commonlyknown in the art, including chemical modification of a compound known tobe effective in altering polynucleotide expression; selection from anexisting, commercially-available or proprietary library ofnaturally-occurring or non-natural chemical compounds; rational designof a compound based on chemical and/or structural properties of thetarget polynucleotide; and selection from a library of chemicalcompounds created combinatorially or randomly. A sample comprising apolynucleotide encoding GCREC is exposed to at least one test compoundthus obtained. The sample may comprise, for example, an intact orpermeabilized cell, or an in vitro cell-free or reconstitutedbiochemical system. Alterations in the expression of a polynucleotideencoding GCREC are assayed by any method commonly known in the art.Typically, the expression of a specific nucleotide is detected byhybridization with a probe having a nucleotide sequence complementary tothe sequence of the polynucleotide encoding GCREC. The amount ofhybridization may be quantified, thus forming the basis for a comparisonof the expression of the polynucleotide both with and without exposureto one or more test compounds. Detection of a change in the expressionof a polynucleotide exposed to a test compound indicates that the testcompound is effective in altering the expression of the polynucleotide.A screen for a compound effective in altering expression of a specificpolynucleotide can be carried out, for example, using aSchizosaccharomyces pombe gene expression system (Atkins, D. et al.(1999) U.S. Pat. No. 5,932,435; Arndt, G. M. et al. (2000) Nucleic AcidsRes. 28:E15) or a human cell line such as HeLa cell (Clarke, M. L. etal. (2000) Biochem. Biophys. Res. Commun. 268:8-13). A particularembodiment of the present invention involves screening a combinatoriallibrary of oligonucleotides (such as deoxyribonucleotides,ribonucleotides, peptide nucleic acids, and modified oligonucleotides)for antisense activity against a specific polynucleotide sequence(Bruice, T. W. et al. (1997) U.S. Pat. No. 5,686,242; Bruice, T. W. etal. (2000) U.S. Pat. No. 6,022,691).

[0229] Many methods for introducing vectors into cells or tissues areavailable and equally suitable for use in vivo, in vitro, and ex vivo.For ex vivo therapy, vectors may be introduced into stem cells takenfrom the patient and clonally propagated for autologous transplant backinto that same patient. Delivery by transfection, by liposomeinjections, or by polycationic amino polymers may be achieved usingmethods which are well known in the art. (See, e.g., Goldman, C. K. etal. (1997) Nat. Biotechnol. 15:462-466.)

[0230] Any of the therapeutic methods described above may be applied toany subject in need of such therapy, including, for example, mammalssuch as humans, dogs, cats, cows, horses, rabbits, and monkeys.

[0231] An additional embodiment of the invention relates to theadministration of a composition which generally comprises an activeingredient formulated with a pharmaceutically acceptable excipient.Excipients may include, for example, sugars, starches, celluloses, gums,and proteins. Various formulations are commonly known and are thoroughlydiscussed in the latest edition of Remington's Pharmaceutical Sciences(Maack Publishing, Easton Pa.). Such compositions may consist of GCREC,antibodies to GCREC, and mimetics, agonists, antagonists, or inhibitorsof GCREC.

[0232] The compositions utilized in this invention may be administeredby any number of routes including, but not limited to, oral,intravenous, intramuscular, intra-arterial, intramedullary, intrathecal,intraventricular, pulmonary, transdermal, subcutaneous, intraperitoneal,intranasal, enteral, topical, sublingual, or rectal means.

[0233] Compositions for pulmonary administration may be prepared inliquid or dry powder form. These compositions are generally aerosolizedimmediately prior to inhalation by the patient. In the case of smallmolecules (e.g. traditional low molecular weight organic drugs), aerosoldelivery of fast-acting formulations is well-known in the art. In thecase of macromolecules (e.g. larger peptides and proteins), recentdevelopments in the field of pulmonary delivery via the alveolar regionof the lung have enabled the practical delivery of drugs such as insulinto blood circulation (see, e.g., Patton, J. S. et al., U.S. Pat. No.5,997,848). Pulmonary delivery has the advantage of administrationwithout needle injection, and obviates the need for potentially toxicpenetration enhancers.

[0234] Compositions suitable for use in the invention includecompositions wherein the active ingredients are contained in aneffective amount to achieve the intended purpose. The determination ofan effective dose is well within the capability of those skilled in theart.

[0235] Specialized forms of compositions may be prepared for directintracellular delivery of macromolecules comprising GCREC or fragmentsthereof. For example, liposome preparations containing acell-impermeable macromolecule may promote cell fusion and intracellulardelivery of the macromolecule. Alternatively, GCREC or a fragmentthereof may be joined to a short cationic N-terminal portion from theHIV Tat-I protein. Fusion proteins thus generated have been found totransduce into the cells of all tissues, including the brain, in a mousemodel system (Schwarze, S. R. et al. (1999) Science 285:1569-1572).

[0236] For any compound, the therapeutically effective dose can beestimated initially either in cell culture assays, e.g., of neoplasticcells, or in animal models such as mice, rats, rabbits, dogs, monkeys,or pigs. An animal model may also be used to determine the appropriateconcentration range and route of administration. Such information canthen be used to determine useful doses and routes for administration inhumans.

[0237] A therapeutically effective dose refers to that amount of activeingredient, for example GCREC or fragments thereof, antibodies of GCREC,and agonists, antagonists or inhibitors of GCREC, which ameliorates thesymptoms or condition. Therapeutic efficacy and toxicity may bedetermined by standard pharmaceutical procedures in cell cultures orwith experimental animals, such as by calculating the ED₅₀ (the dosetherapeutically effective in 50% of the population) or LD₅₀ (the doselethal to 50% of the population) statistics. The dose ratio of toxic totherapeutic effects is the therapeutic index, which can be expressed asthe LD₅₀/ED₅₀ ratio. Compositions which exhibit large therapeuticindices are preferred. The data obtained from cell culture assays andanimal studies are used to formulate a range of dosage for human use.The dosage contained in such compositions is preferably within a rangeof circulating concentrations that includes the ED₅₀ with little or notoxicity. The dosage varies within this range depending upon the dosageform employed, the sensitivity of the patient, and the route ofadministration.

[0238] The exact dosage will be determined by the practitioner, in lightof factors related to the subject requiring treatment. Dosage andadministration are adjusted to provide sufficient levels of the activemoiety or to maintain the desired effect. Factors which may be takeninto account include the severity of the disease state, the generalhealth of the subject, the age, weight, and gender of the subject, timeand frequency of administration, drug combination(s), reactionsensitivities, and response to therapy. Long-acting compositions may beadministered every 3 to 4 days, every week, or biweekly depending on thehalf-life and clearance rate of the particular formulation.

[0239] Normal dosage amounts may vary from about 0.1 μg to 100,000 μg,up to a total dose of about 1 gram, depending upon the route ofadministration. Guidance as to particular dosages and methods ofdelivery is provided in the literature and generally available topractitioners in the art. Those skilled in the art will employ differentformulations for nucleotides than for proteins or their inhibitors.Similarly, delivery of polynucleotides or polypeptides will be specificto particular cells, conditions, locations, etc.

[0240] Diagnostics

[0241] In another embodiment, antibodies which specifically bind GCRECmay be used for the diagnosis of disorders characterized by expressionof GCREC, or in assays to monitor patients being treated with GCREC oragonists, antagonists, or inhibitors of GCREC. Antibodies useful fordiagnostic purposes may be prepared in the same manner as describedabove for therapeutics. Diagnostic assays for GCREC include methodswhich utilize the antibody and a label to detect GCREC in human bodyfluids or in extracts of cells or tissues. The antibodies may be usedwith or without modification, and may be labeled by covalent ornon-covalent attachment of a reporter molecule. A wide variety ofreporter molecules, several of which are described above, are known inthe art and may be used.

[0242] A variety of protocols for measuring GCREC, including ELISAs,RIAs, and FACS, are known in the art and provide a basis for diagnosingaltered or abnormal levels of GCREC expression. Normal or standardvalues for GCREC expression are established by combining body fluids orcell extracts taken from normal mammalian subjects, for example, humansubjects, with antibodies to GCREC under conditions suitable for complexformation. The amount of standard complex formation may be quantitatedby various methods, such as photometric means. Quantities of GCRECexpressed in subject, control, and disease samples from biopsied tissuesare compared with the standard values. Deviation between standard andsubject values establishes the parameters for diagnosing disease.

[0243] In another embodiment of the invention, the polynucleotidesencoding GCREC may be used for diagnostic purposes. The polynucleotideswhich may be used include oligonucleotide sequences, complementary RNAand DNA molecules, and PNAs. The polynucleotides may be used to detectand quantify gene expression in biopsied tissues in which expression ofGCREC may be correlated with disease. The diagnostic assay may be usedto determine absence, presence, and excess expression of GCREC, and tomonitor regulation of GCREC levels during therapeutic intervention.

[0244] In one aspect, hybridization with PCR probes which are capable ofdetecting polynucleotide sequences, including genomic sequences,encoding GCREC or closely related molecules may be used to identifynucleic acid sequences which encode GCREC. The specificity of the probe,whether it is made from a highly specific region, e.g., the 5′regulatory region, or from a less specific region, e.g., a conservedmotif, and the stringency of the hybridization or amplification willdetermine whether the probe identifies only naturally occurringsequences encoding GCREC, allelic variants, or related sequences.

[0245] Probes may also be used for the detection of related sequences,and may have at least 50% sequence identity to any of the GCREC encodingsequences. The hybridization probes of the subject invention may be DNAor RNA and may be derived from the sequence of SEQ ID NO:49-96 or fromgenomic sequences including promoters, enhancers, and introns of theGCREC gene.

[0246] Means for producing specific hybridization probes for DNAsencoding GCREC include the cloning of polynucleotide sequences encodingGCREC or GCREC derivatives into vectors for the production of mRNAprobes. Such vectors are known in the art, are commercially available,and may be used to synthesize RNA probes in vitro by means of theaddition of the appropriate RNA polymerases and the appropriate labelednucleotides. Hybridization probes may be labeled by a variety ofreporter groups, for example, by radionuclides such as ³²P or ³⁵S, or byenzymatic labels, such as alkaline phosphatase coupled to the probe viaavidin/biotin coupling systems, and the like.

[0247] Polynucleotide sequences encoding GCREC may be used for thediagnosis of disorders associated with expression of GCREC. Examples ofsuch disorders include, but are not limited to, a cell proliferativedisorder such as actinic keratosis, arteriosclerosis, atherosclerosis,bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD),myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera,psoriasis, primary thrombocythemia, and cancers includingadenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma,teratocarcinoma, and, in particular, cancers of the adrenal gland,bladder, bone, bone marrow, brain, breast, cervix, gall bladder,ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle,ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin,spleen, testis, thymus, thyroid, and uterus; a neurological disordersuch as epilepsy, ischemic cerebrovascular disease, stroke, cerebralneoplasms, Alzheimer's disease, Pick's disease, Huntington's disease,dementia, Parkinson's disease and other extrapyramidal disorders,amyotrophic lateral sclerosis and other motor neuron disorders,progressive neural muscular atrophy, retinitis pigmentosa, hereditaryataxias, multiple sclerosis and other demyelinating diseases, bacterialand viral meningitis, brain abscess, subdural empyema, epidural abscess,suppurative intracranial thrombophlebitis, myelitis and radiculitis,viral central nervous system disease, prion diseases including kuru,Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome,fatal familial insomnia, nutritional and metabolic diseases of thenervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinalhemangioblastomatosis, encephalotrigeminal syndrome, mental retardationand other developmental disorders of the central nervous system,cerebral palsy, neuroskeletal disorders, autonomic nervous systemdisorders, cranial nerve disorders, spinal cord diseases, musculardystrophy and other neuromuscular disorders, peripheral nervous systemdisorders, dermatomyositis and polymyositis, inherited, metabolic,endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis,mental disorders including mood, anxiety, and schizophrenic disorders,seasonal affective disorder (SAD), akathesia, amnesia, catatonia,diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses,postherpetic neuralgia, Tourette's disorder, progressive supranuclearpalsy, corticobasal degeneration, and familial frontotemporal dementia;a cardiovascular disorder such as arteriovenous fistula,atherosclerosis, hypertension, vasculitis, Raynaud's disease, aneurysms,arterial dissections, varicose veins, thrombophlebitis andphlebothrombosis, vascular tumors, complications of thrombolysis,balloon angioplasty, vascular replacement, and coronary artery bypassgraft surgery, congestive heart failure, ischemic heart disease, anginapectoris, myocardial infarction, hypertensive heart disease,degenerative valvular heart disease, calcific aortic valve stenosis,congenitally bicuspid aortic valve, mitral annular calcification, mitralvalve prolapse, rheumatic fever and rheumatic heart disease, infectiveendocarditis, nonbacterial thrombotic endocarditis, endocarditis ofsystemic lupus erythematosus, carcinoid heart disease, cardiomyopathy,myocarditis, pericarditis, neoplastic heart disease, congenital heartdisease, and complications of cardiac transplantation; agastrointestinal disorder such as dysphagia, peptic esophagitis,esophageal spasm, esophageal stricture, esophageal carcinoma, dyspepsia,indigestion, gastritis, gastric carcinoma, anorexia, nausea, emesis,gastroparesis, antral or pyloric edema, abdominal angina, pyrosis,gastroenteritis, intestinal obstruction, infections of the intestinaltract, peptic ulcer, cholelithiasis, cholecystitis, cholestasis,pancreatitis, pancreatic carcinoma, biliary tract disease, hepatitis,hyperbilirubinemia, cirrhosis, passive congestion of the liver,hepatoma, infectious colitis, ulcerative colitis, ulcerative proctitis,Crohn's disease, Whipple's disease, Mallory-Weiss syndrome, coloniccarcinoma, colonic obstruction, irritable bowel syndrome, short bowelsyndrome, diarrhea, constipation, gastrointestinal hemorrhage, acquiredimmunodeficiency syndrome (AIDS) enteropathy, jaundice, hepaticencephalopathy, hepatorenal syndrome, hepatic steatosis,hemochromatosis, Wilson's disease, alpha₁-antitrypsin deficiency, Reye'ssyndrome, primary sclerosing cholangitis,.liver infarction, portal veinobstruction and thrombosis, centrilobular necrosis, peliosis hepatis,hepatic vein thrombosis, veno-occlusive disease, preeclampsia,eclampsia, acute fatty liver of pregnancy, intrahepatic cholestasis ofpregnancy, and hepatic tumors including nodular hyperplasias, adenomas,and carcinomas; an autoimmune/inflammatory disorder such as acquiredimmunodeficiency syndrome (AIDS), Addison's disease, adult respiratorydistress syndrome, allergies, ankylosing spondylitis, amyloidosis,anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmunethyroiditis, autoimmune polyendocrinopathy-candidiasis-ectodermaldystrophy (APECED), bronchitis, cholecystitis, contact dermatitis,Crohn's disease, atopic dermatitis, dermatomyositis, diabetes mellitus,emphysema, episodic lymphopenia with lymphocytotoxins, erythroblastosisfetalis, erythema nodosum, atrophic gastritis, glomerulonephritis,Goodpasture's syndrome, gout, Graves' disease, Hashimoto's thyroiditis,hypereosinophilia, irritable bowel syndrome, multiple sclerosis,myasthenia gravis, myocardial or pericardial inflammation,osteoarthritis, osteoporosis, pancreatitis, polymyositis, psoriasis,Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjögren'ssyndrome, systemic anaphylaxis, systemic lupus erythematosus, systemicsclerosis, thrombocytopenic purpura, ulcerative colitis, uveitis, Wernersyndrome, complications of cancer, hemodialysis, and extracorporealcirculation, viral, bacterial, fungal, parasitic, protozoal, andhelminthic infections, and trauma; a metabolic disorder such asdiabetes, obesity, and osteoporosis; and an infection by a viral agentclassified as adenovirus, arenavirus, bunyavirus, calicivirus,coronavirus, filovirus, hepadnavirus, herpesvirus, flavivirus,orthomyxovirus, parvovirus, papovavirus, paramyxovirus, picornavirus,poxvirus, reovirus, retrovirus, rhabdovirus, and tongavirus. Thepolynucleotide sequences encoding GCREC may be used in Southern ornorthern analysis, dot blot, or other membrane-based technologies; inPCR technologies; in dipstick, pin, and multiformat ELISA-like assays;and in microarrays utilizing fluids or tissues from patients to detectaltered GCREC expression. Such qualitative or quantitative methods arewell known in the art.

[0248] In a particular aspect, the nucleotide sequences encoding GCRECmay be useful in assays that detect the presence of associateddisorders, particularly those mentioned above. The nucleotide sequencesencoding GCREC may be labeled by standard methods and added to a fluidor tissue sample from a patient under conditions suitable for theformation of hybridization complexes. After a suitable incubationperiod, the sample is washed and the signal is quantified and comparedwith a standard value. If the amount of signal in the patient sample issignificantly altered in comparison to a control sample then thepresence of altered levels of nucleotide sequences encoding GCREC in thesample indicates the presence of the associated disorder. Such assaysmay also be used to evaluate the efficacy of a particular therapeutictreatment regimen in animal studies, in clinical trials, or to monitorthe treatment of an individual patient.

[0249] In order to provide a basis for the diagnosis of a disorderassociated with expression of GCREC, a normal or standard profile forexpression is established. This may be accomplished by combining bodyfluids or cell extracts taken from normal subjects, either animal orhuman, with a sequence, or a fragment thereof, encoding GCREC, underconditions suitable for hybridization or amplification. Standardhybridization may be quantified by comparing the values obtained fromnormal subjects with values from an experiment in which a known amountof a substantially purified polynucleotide is used. Standard valuesobtained in this manner may be compared with values obtained fromsamples from patients who are symptomatic for a disorder. Deviation fromstandard values is used to establish the presence of a disorder.

[0250] Once the presence of a disorder is established and a treatmentprotocol is initiated, hybridization assays may be repeated on a regularbasis to determine if the level of expression in the patient begins toapproximate that which is observed in the normal subject. The resultsobtained from successive assays may be used to show the efficacy oftreatment over a period ranging from several days to months.

[0251] With respect to cancer, the presence of an abnormal amount oftranscript (either under- or overexpressed) in biopsied tissue from anindividual may indicate a predisposition for the development of thedisease, or may provide a means for detecting the disease prior to theappearance of actual clinical symptoms. A more definitive diagnosis ofthis type may allow health professionals to employ preventative measuresor aggressive treatment earlier thereby preventing the development orfurther progression of the cancer.

[0252] Additional diagnostic uses for oligonucleotides designed from thesequences encoding GCREC may involve the use of PCR. These oligomers maybe chemically synthesized, generated enzymatically, or produced invitro. Oligomers will preferably contain a fragment of a polynucleotideencoding GCREC, or a fragment of a polynucleotide complementary to thepolynucleotide encoding GCREC, and will be employed under optimizedconditions for identification of a specific gene or condition. Oligomersmay also be employed under less stringent conditions for detection orquantification of closely related DNA or RNA sequences.

[0253] In a particular aspect, oligonucleotide primers derived from thepolynucleotide sequences encoding GCREC may be used to detect singlenucleotide polymorphisms (SNPs). SNPs are substitutions, insertions anddeletions that are a frequent cause of inherited or acquired geneticdisease in humans. Methods of SNP detection include, but are not limitedto, single-stranded conformation polymorphism (SSCP) and fluorescentSSCP (fSSCP) methods. In SSCP, oligonucleotide primers derived from thepolynucleotide sequences encoding GCREC are used to amplify DNA usingthe polymerase chain reaction (PCR). The DNA may be derived, forexample, from diseased or normal tissue, biopsy samples, bodily fluids,and the like. SNPs in the DNA cause differences in the secondary andtertiary structures of PCR products in single-stranded form, and thesedifferences are detectable using gel electrophoresis in non-denaturinggels. In fSCCP, the oligonucleotide primers are fluorescently labeled,which allows detection of the amplimers in high-throughput equipmentsuch as DNA sequencing machines. Additionally, sequence databaseanalysis methods, termed in silico SNP (isSNP), are capable ofidentifying polymorphisms by comparing the sequence of individualoverlapping DNA fragments which assemble into a common consensussequence. These computer-based methods filter out sequence variationsdue to laboratory preparation of DNA and sequencing errors usingstatistical models and automated analyses of DNA sequence chromatograms.In the alternative, SNPs may be detected and characterized by massspectrometry using, for example, the high throughput MASSARRAY system(Sequenom, Inc., San Diego Calif.).

[0254] SNPs may be used to study the genetic basis of human disease. Forexample, at least 16 common SNPs have been associated withnon-insulin-dependent diabetes mellitus. SNPs are also useful forexamining differences in disease outcomes in monogenic disorders, suchas cystic fibrosis, sickle cell anemia, or chronic granulomatousdisease. For example, variants in the mannose-binding lectin, MBL2, havebeen shown to be correlated with deleterious pulmonary outcomes incystic fibrosis. SNPs also have utility in pharmacogenomics, theidentification of genetic variants that influence a patient's responseto a drug, such as life-threatening toxicity. For example, a variationin N-acetyl transferase is associated with a high incidence ofperipheral neuropathy in response to the anti-tuberculosis drugisoniazid, while a variation in the core promoter of the ALOX5 generesults in diminished clinical response to treatment with ananti-asthmna drug that targets the 5-lipoxygenase pathway. Analysis ofthe distribution of SNPs in different populations is useful forinvestigating genetic drift, mutation, recombination, and selection, aswell as for tracing the origins of populations and their migrations.(Taylor, J. G. et al. (2001) Trends Mol. Med. 7:507-512; Kwok, P. -Y.and Z. Gu (1999) Mol. Med. Today 5:538-543; Nowotny, P. et al. (2001)Curr. Opin. Neurobiol. 11:637-641.)

[0255] Methods which may also be used to quantify the expression ofGCREC include radiolabeling or biotinylating nucleotides,coamplification of a control nucleic acid, and interpolating resultsfrom standard curves. (See, e.g., Melby, P. C. et al. (1993) J. Immunol.Methods 159:235-244; Duplaa, C. et al. (1993) Anal. Biochem.212:229-236.) The speed of quantitation of multiple samples may beaccelerated by running the assay in a high-throughput format where theoligomer or polynucleotide of interest is presented in various dilutionsand a spectrophotometric or colorimetric response gives rapidquantitation.

[0256] In further embodiments, oligonucleotides or longer fragmentsderived from any of the polynucleotide sequences described herein may beused as elements on a microarray. The microarray can be used intranscript imaging techniques which monitor the relative expressionlevels of large numbers of genes simultaneously as described below. Themicroarray may also be used to identify genetic variants, mutations, andpolymorphisms. This information may be used to determine gene function,to understand the genetic basis of a disorder, to diagnose a disorder,to monitor progression/regression of disease as a function of geneexpression, and to develop and monitor the activities of therapeuticagents in the treatment of disease. In particular, this information maybe used to develop a pharmacogenomic profile of a patient in order toselect the most appropriate and effective treatment regimen for thatpatient. For example, therapeutic agents which are highly effective anddisplay the fewest side effects may be selected for a patient based onhis/her pharmacogenomic profile.

[0257] In another embodiment, GCREC, fragments of GCREC, or antibodiesspecific for GCREC may be used as elements on a microarray. Themicroarray may be used to monitor or measure protein-proteininteractions, drug-target interactions, and gene expression profiles, asdescribed above.

[0258] A particular embodiment relates to the use of the polynucleotidesof the present invention to generate a transcript image of a tissue orcell type. A transcript image represents the global pattern of geneexpression by a particular tissue or cell type. Global gene expressionpatterns are analyzed by quantifying the number of expressed genes andtheir relative abundance under given conditions and at a given time.(See Seilhamer et al., “Comparative Gene Transcript Analysis,” U.S. Pat.No. 5,840,484, expressly incorporated by reference herein.) Thus atranscript image may be generated by hybridizing the polynucleotides ofthe present invention or their complements to the totality oftranscripts or reverse transcripts of a particular tissue or cell type.In one embodiment, the hybridization takes place in high-throughputformat, wherein the polynucleotides of the present invention or theircomplements comprise a subset of a plurality of elements on amicroarray. The resultant transcript image would provide a profile ofgene activity.

[0259] Transcript images may be generated using transcripts isolatedfrom tissues, cell lines, biopsies, or other biological samples. Thetranscript image may thus reflect gene expression in vivo, as in thecase of a tissue or biopsy sample, or in vitro, as in the case of a cellline.

[0260] Transcript images which profile the expression of thepolynucleotides of the present invention may also be used in conjunctionwith in vitro model systems and preclinical evaluation ofpharmaceuticals, as well as toxicological testing of industrial andnaturally-occurring environmental compounds. All compounds inducecharacteristic gene expression patterns, frequently termed molecularfingerprints or toxicant signatures, which are indicative of mechanismsof action and toxicity (Nuwaysir, E. F. et al. (1999) Mol. Carcinog.24:153-159; Steiner, S. and N. L. Anderson (2000) Toxicol. Lett.112-113:467-471, expressly incorporated by reference herein). If a testcompound has a signature similar to that of a compound with knowntoxicity, it is likely to share those toxic properties. Thesefingerprints or signatures are most useful and refined when they containexpression information from a large number of genes and gene families.Ideally, a genome-wide measurement of expression provides the highestquality signature. Even genes whose expression is not altered by anytested compounds are important as well, as the levels of expression ofthese genes are used to normalize the rest of the expression data. Thenormalization procedure is useful for comparison of expression dataafter treatment with different compounds. While the assignment of genefunction to elements of a toxicant signature aids in interpretation oftoxicity mechanisms, knowledge of gene function is not necessary for thestatistical matching of signatures which leads to prediction oftoxicity. (See, for example, Press Release 00-02 from the NationalInstitute of Environmental Health Sciences, released Feb. 29, 2000,available at http://www.niehs.nih.gov/oc/news/toxchip.htm.) Therefore,it is important and desirable in toxicological screening using toxicantsignatures to include all expressed gene sequences.

[0261] In one embodiment, the toxicity of a test compound is assessed bytreating a biological sample containing nucleic acids with the testcompound. Nucleic acids that are expressed in the treated biologicalsample are hybridized with one or more probes specific to thepolynucleotides of the present invention, so that transcript levelscorresponding to the polynucleotides of the present invention may bequantified. The transcript levels in the treated biological sample arecompared with levels in an untreated biological sample. Differences inthe transcript levels between the two samples are indicative of a toxicresponse caused by the test compound in the treated sample.

[0262] Another particular embodiment relates to the use of thepolypeptide sequences of the present invention to analyze the proteomeof a tissue or cell type. The term proteome refers to the global patternof protein expression in a particular tissue or cell type. Each proteincomponent of a proteome can be subjected individually to furtheranalysis. Proteome expression patterns, or profiles, are analyzed byquantifying the number of expressed proteins and their relativeabundance under given conditions and at a given time. A profile of acell's proteome may thus be generated by separating and analyzing thepolypeptides of a particular tissue or cell type. In one embodiment, theseparation is achieved using two-dimensional gel electrophoresis, inwhich proteins from a sample are separated by isoelectric focusing inthe first dimension, and then according to molecular weight by sodiumdodecyl sulfate slab gel electrophoresis in the second dimension(Steiner and Anderson, supra). The proteins are visualized in the gel asdiscrete and uniquely positioned spots, typically by staining the gelwith an agent such as Coomassie Blue or silver or fluorescent stains.The optical density of each protein spot is generally proportional tothe level of the protein in the sample. The optical densities ofequivalently positioned protein spots from different samples, forexample, from biological samples either treated or untreated with a testcompound or therapeutic agent, are compared to identify any changes inprotein spot density related to the treatment. The proteins in the spotsare partially sequenced using, for example, standard methods employingchemical or enzymatic cleavage followed by mass spectrometry. Theidentity of the protein in a spot may be determined by comparing itspartial sequence, preferably of at least 5 contiguous amino acidresidues, to the polypeptide sequences of the present invention. In somecases, further sequence data may be obtained for definitive proteinidentification.

[0263] A proteomic profile may also be generated using antibodiesspecific for GCREC to quantify the levels of GCREC expression. In oneembodiment, the antibodies are used as elements on a microarray, andprotein expression levels are quantified by exposing the microarray tothe sample and detecting the levels of protein bound to each arrayelement (Lueking, A. et al. (1999) Anal. Biochem. 270:103-111; Mendoze,L. G. et al. (1999) Biotechniques 27:778-788). Detection may beperformed by a variety of methods known in the art, for example, byreacting the proteins in the sample with a thiol- or amino-reactivefluorescent compound and detecting the amount of fluorescence bound ateach array element.

[0264] Toxicant signatures at the proteome level are also useful fortoxicological screening, and should be analyzed in parallel withtoxicant signatures at the transcript level. There is a poor correlationbetween transcript and protein abundances for some proteins in sometissues (Anderson, N. L. and J. Seilhamer (1997) Electrophoresis18:533-537), so proteome toxicant signatures may be useful in theanalysis of compounds which do not significantly affect the transcriptimage, but which alter the proteomic profile. In addition, the analysisof transcripts in body fluids is difficult, due to rapid degradation ofmRNA, so proteomic profiling may be more reliable and informative insuch cases.

[0265] In another embodiment, the toxicity of a test compound isassessed by treating a biological sample containing proteins with thetest compound. Proteins that are expressed in the treated biologicalsample are separated so that the amount of each protein can bequantified. The amount of each protein is compared to the amount of thecorresponding protein in an untreated biological sample. A difference inthe amount of protein between the two samples is indicative of a toxicresponse to the test compound in the treated sample. Individual proteinsare identified by sequencing the amino acid residues of the individualproteins and comparing these partial sequences to the polypeptides ofthe present invention.

[0266] In another embodiment, the toxicity of a test compound isassessed by treating a biological sample containing proteins with thetest compound. Proteins from the biological sample are incubated withantibodies specific to the polypeptides of the present invention. Theamount of protein recognized by the antibodies is quantified. The amountof protein in the treated biological sample is compared with the amountin an untreated biological sample. A difference in the amount of proteinbetween the two samples is indicative of a toxic response to the testcompound in the treated sample.

[0267] Microarrays may be prepared, used, and analyzed using methodsknown in the art. (See, e.g., Brennan, T. M. et al. (1995) U.S. Pat. No.5,474,796; Schena, M. et al. (1996) Proc. Natl. Acad. Sci. USA93:10614-10619; Baldeschweiler et al. (1995) PCT applicationWO95/251116; Shalon, D. et al. (1995) PCT application WO95/35505;Heller, R. A. et al. (1997) Proc. Natl. Acad. Sci. USA 94:2150-2155; andHeller, M. J. et al. (1997) U.S. Pat. No. 5,605,662.) Various types ofmicroarrays are well known and thoroughly described in DNA Microarrays:A Practical Approach, M. Schena, ed. (1999) Oxford University Press,London, hereby expressly incorporated by reference.

[0268] In another embodiment of the invention, nucleic acid sequencesencoding GCREC may be used to generate hybridization probes useful inmapping the naturally occurring genomic sequence. Either coding ornoncoding sequences may be used, and in some instances, noncodingsequences may be preferable over coding sequences. For example,conservation of a coding sequence among members of a multi-gene familymay potentially cause undesired cross hybridization during chromosomalmapping. The sequences may be mapped to a particular chromosome, to aspecific region of a chromosome, or to artificial chromosomeconstructions, e.g., human artificial chromosomes (HACs), yeastartificial chromosomes (YACs), bacterial artificial chromosomes (BACs),bacterial P1 constructions, or single chromosome cDNA libraries. (See,e.g., Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355; Price, C.M. (1993) Blood Rev. 7:127-134; and Trask, B. J. (1991) Trends Genet.7:149-154.) Once mapped, the nucleic acid sequences of the invention maybe used to develop genetic linkage maps, for example, which correlatethe inheritance of a disease state with the inheritance of a particularchromosome region or restriction fragment length polymorphism (RFLP).(See, for example, Lander, E. S. and D. Botstein (1986) Proc. Natl.Acad. Sci. USA 83:7353-7357.)

[0269] Fluorescent in situ hybridization (FISH) may be correlated withother physical and genetic map data. (See, e.g., Heinz-Ulrich, et al.(1995) in Meyers, supra, pp. 965-968.) Examples of genetic map data canbe found in various scientific journals or at the Online MendelianInheritance in Man (OMIM) World Wide Web site. Correlation between thelocation of the gene encoding GCREC on a physical map and a specificdisorder, or a predisposition to a specific disorder, may help definethe region of DNA associated with that disorder and thus may furtherpositional cloning efforts.

[0270] In situ hybridization of chromosomal preparations and physicalmapping techniques, such as linkage analysis using establishedchromosomal markers, may be used for extending genetic maps. Often theplacement of a gene on the chromosome of another mammalian species, suchas mouse, may reveal associated markers even if the exact chromosomallocus is not known. This information is valuable to investigatorssearching for disease genes using positional cloning or other genediscovery techniques. Once the gene or genes responsible for a diseaseor syndrome have been crudely localized by genetic linkage to aparticular genomic region, e.g., ataxia-telangiectasia to 11q22-23, anysequences mapping to that area may represent associated or regulatorygenes for further investigation. (See, e.g., Gatti, R. A. et al. (1988)Nature 336:577-580.) The nucleotide sequence of the instant inventionmay also be used to detect differences in the chromosomal location dueto translocation, inversion, etc., among normal, carrier, or affectedindividuals.

[0271] In another embodiment of the invention, GCREC, its catalytic orimmunogenic fragments, or oligopeptides thereof can be used forscreening libraries of compounds in any of a variety of drug screeningtechniques. The fragment employed in such screening may be free insolution, affixed to a solid support, borne on a cell surface, orlocated intracellularly. The formation of binding complexes betweenGCREC and the agent being tested may be measured.

[0272] Another technique for drug screening provides for high throughputscreening of compounds having suitable binding affinity to the proteinof interest. (See, e.g., Geysen, et al. (1984) PCT applicationWO84/03564.) In this method, large numbers of different small testcompounds are synthesized on a solid substrate. The test compounds arereacted with GCREC, or fragments thereof, and washed. Bound GCREC isthen detected by methods well known in the art. Purified GCREC can alsobe coated directly onto plates for use in the aforementioned drugscreening techniques. Alternatively, non-neutralizing antibodies can beused to capture the peptide and immobilize it on a solid support.

[0273] In another embodiment, one may use competitive drug screeningassays in which neutralizing antibodies capable of binding GCRECspecifically compete with a test compound for binding GCREC. In thismanner, antibodies can be used to detect the presence of any peptidewhich shares one or more antigenic determinants with GCREC.

[0274] In additional embodiments, the nucleotide sequences which encodeGCREC may be used in any molecular biology techniques that have yet tobe developed, provided the new techniques rely on properties ofnucleotide sequences that are currently known, including, but notlimited to, such properties as the triplet genetic code and specificbase pair interactions.

[0275] Without further elaboration, it is believed that one skilled inthe art can, using the preceding description, utilize the presentinvention to its fullest extent. The following embodiments are,therefore, to be construed as merely illustrative, and not limitative ofthe remainder of the disclosure in any way whatsoever.

[0276] The disclosures of all patents, applications and publications,mentioned above and below, including U.S. Ser. No. 60/267,322, U.S. Ser.No. 60/271,215, U.S. Ser. No. 60/274,551, U.S. Ser. No. 60/278,507, U.S.Ser. No. 60/280,597, U.S. Ser. No. 60/281,107, and No. U.S. Ser. No.60/282,121, are expressly incorporated by reference herein.

EXAMPLES

[0277] I. Construction of cDNA Libraries

[0278] Incyte cDNAs were derived from cDNA libraries described in theLIFESEQ GOLD database (Incyte Genomics, Palo Alto Calif.). Some tissueswere homogenized and lysed in guanidinium isothiocyanate, while otherswere homogenized and lysed in phenol or in a suitable mixture ofdenaturants, such as TRIZOL (Life Technologies), a monophasic solutionof phenol and guanidine isothiocyanate. The resulting lysates werecentrifuged over CsCl cushions or extracted with chloroform. RNA wasprecipitated from the lysates with either isopropanol or sodium acetateand ethanol, or by other routine methods.

[0279] Phenol extraction and precipitation of RNA were repeated asnecessary to increase RNA purity. In some cases, RNA was treated withDNase. For most libraries, poly(A)+ RNA was isolated using oligod(T)-coupled paramagnetic particles (Promega), OLIGOTEX latex particles(QIAGEN, Chatsworth Calif.), or an OLIGOTEX mRNA purification kit(QIAGEN). Alternatively, RNA was isolated directly from tissue lysatesusing other RNA isolation kits, e.g., the POLY(A)PURE mRNA purificationkit (Ambion, Austin Tex.).

[0280] In some cases, Stratagene was provided with RNA and constructedthe corresponding cDNA libraries. Otherwise, cDNA was synthesized andcDNA libraries were constructed with the UNIZAP vector system(Stratagene) or SUPERSCRIPT plasmid system (Life Technologies), usingthe recommended procedures or similar methods known in the art. (See,e.g., Ausubel, 1997, supra, units 5.1-6.6.) Reverse transcription wasinitiated using oligo d(T) or random primers. Synthetic oligonucleotideadapters were ligated to double stranded cDNA, and the cDNA was digestedwith the appropriate restriction enzyme or enzymes. For most libraries,the cDNA was size-selected (300-1000 bp) using SEPHACRYL S1000,SEPHAROSE CL2B, or SEPHAROSE CL4B column chromatography (AmershamPharmacia Biotech) or preparative agarose gel electrophoresis. cDNAswere ligated into compatible restriction enzyme sites of the polylinkerof a suitable plasmid, e.g., PBLUESCRIPT plasmid (Stratagene), PSPORT1plasmid (Life Technologies), PCDNA2.1 plasmid (Invitrogen, CarlsbadCalif.), PBK-CMV plasmid (Stratagene), PCR2-TOPOTA plasmid (Invitrogen),PCMV-ICIS plasmid (Stratagene), pIGEN (Incyte Genomics, Palo AltoCalif.), pRARE (Incyte Genomics), or pINCY (Incyte Genomics), orderivatives thereof. Recombinant plasmids were transformed intocompetent E. coli cells including XL1-Blue, XL1-BlueMRF, or SOLR fromStratagene or DH5α, DH10B, or ElectroMAX DH10B from Life Technologies.

[0281] II. Isolation of cDNA Clones

[0282] Plasmids obtained as described in Example I were recovered fromhost cells by in vivo excision using the UNIZAP vector system(Stratagene) or by cell lysis. Plasmids were purified using at least oneof the following: a Magic or WIZARD Minipreps DNA purification system(Promega); an AGTC Miniprep purification kit (Edge Biosystems,Gaithersburg Md.); and QIAWELL 8 Plasmid, QIAWELL 8 Plus Plasmid,QIAWELL 8 Ultra Plasmid purification systems or the R.E.A.L. PREP 96plasmid purification kit from QIAGEN. Following precipitation, plasmidswere resuspended in 0.1 ml of distilled water and stored, with orwithout lyophilization, at 4° C.

[0283] Alternatively, plasmid DNA was amplified from host cell lysatesusing direct link PCR in a high-throughput format (Rao, V. B. (1994)Anal. Biochem. 216:1-14). Host cell lysis and thermal cycling steps werecarried out in a single reaction mixture. Samples were processed andstored in 384-well plates, and the concentration of amplified plasmidDNA was quantified fluorometrically using PICOGREEN dye (MolecularProbes, Eugene Oreg.) and a FLUOROSKAN II fluorescence scanner(Labsystems Oy, Helsinki, Finland).

[0284] III. Sequencing and Analysis

[0285] Incyte cDNA recovered in plasmids as described in Example II weresequenced as follows. Sequencing reactions were processed using standardmethods or high-throughput instrumentation such as the ABI CATALYST 800(Applied Biosystems) thermal cycler or the PTC-200 thermal cycler (MJResearch) in conjunction with the HYDRA microdispenser (RobbinsScientific) or the MICROLAB 2200 (Hamilton) liquid transfer system. cDNAsequencing reactions were prepared using reagents provided by AmershamPharmacia Biotech or supplied in ABI sequencing kits such as the ABIPRISM BIGDYE Terminator cycle sequencing ready reaction kit (AppliedBiosystems). Electrophoretic separation of cDNA sequencing reactions anddetection of labeled polynucleotides were carried out using the MEGABACE1000 DNA sequencing system (Molecular Dynamics); the ABI PRISM 373 or377 sequencing system (Applied Biosystems) in conjunction with standardABI protocols and base calling software; or other sequence analysissystems known in the art. Reading frames within the cDNA sequences wereidentified using standard methods (reviewed in Ausubel, 1997, supra,unit 7.7). Some of the cDNA sequences were selected for extension usingthe techniques disclosed in Example VIII.

[0286] The polynucleotide sequences derived from Incyte cDNAs werevalidated by removing vector, linker, and poly(A) sequences and bymasking ambiguous bases, using algorithms and programs based on BLAST,dynamic programming, and dinucleotide nearest neighbor analysis. TheIncyte cDNA sequences or translations thereof were then queried againsta selection of public databases such as the GenBank primate, rodent,mammalian, vertebrate, and eukaryote databases, and BLOCKS, PRINTS,DOMO, PRODOM; PROTEOME databases with sequences from Homo sapiens,Rattus norvepicus, Mus musculus, Caenorhabditis elegans, Saccharomycescerevisiae, Schizosaccharomyces pombe, and Candida albicans (IncyteGenomics, Palo Alto Calif.); hidden Markov model (HMM)-based proteinfamily databases such as PFAM; and HMM-based protein domain databasessuch as SMART (Schultz et al. (1998) Proc. Natl. Acad. Sci. USA95:5857-5864; Letunic, I. et al. (2002) Nucleic Acids Res. 30:242-244).(HMM is a probabilistic approach which analyzes consensus primarystructures of gene families. See, for example, Eddy, S. R. (1996) Curr.Opin. Struct. Biol. 6:361-365.) The queries were performed usingprograms based on BLAST, FASTA, BLIMPS, and HMMER. The Incyte cDNAsequences were assembled to produce full length polynucleotidesequences. Alternatively, GenBank cDNAs, GenBank ESTs, stitchedsequences, stretched sequences, or Genscan-predicted coding sequences(see Examples IV and V) were used to extend Incyte cDNA assemblages tofull length. Assembly was performed using programs based on Phred,Phrap, and Consed, and cDNA assemblages were screened for open readingframes using programs based on GeneMark, BLAST, and FASTA. The fulllength polynucleotide sequences were translated to derive thecorresponding full length polypeptide sequences. Alternatively, apolypeptide of the invention may begin at any of the methionine residuesof the full length translated polypeptide. Full length polypeptidesequences were subsequently analyzed by querying against databases suchas the GenBank protein databases (genpept), SwissProt, the PROTEOMEdatabases, BLOCKS, PRINTS, DOMO, PRODOM, Prosite, hidden Markov model(HMM)-based protein family databases such as PFAM; and HMM-based proteindomain databases such as SMART. Full length polynucleotide sequences arealso analyzed using MACDNASIS PRO software (Hitachi SoftwareEngineering, South San Francisco Calif.) and LASERGENE software(DNASTAR). Polynucleotide and polypeptide sequence alignments aregenerated using default parameters specified by the CLUSTAL algorithm asincorporated into the MEGALIGN multisequence alignment program(DNASTAR), which also calculates the percent identity between alignedsequences.

[0287] Table 7 summarizes the tools, programs, and algorithms used forthe analysis and assembly of Incyte cDNA and full length sequences andprovides applicable descriptions, references, and threshold parameters.The first column of Table 7 shows the tools, programs, and algorithmsused, the second column provides brief descriptions thereof, the thirdcolumn presents appropriate references, all of which are incorporated byreference herein in their entirety, and the fourth column presents,where applicable, the scores, probability values, and other parametersused to evaluate the strength of a match between two sequences (thehigher the score or the lower the probability value, the greater theidentity between two sequences).

[0288] The programs described above for the assembly and analysis offull length polynucleotide and polypeptide sequences were also used toidentify polynucleotide sequence fragments from SEQ ID NO:49-96.Fragments from about 20 to about 4000 nucleotides which are useful inhybridization and amplification technologies are described in Table 4,column 2.

[0289] IV. Identification and Editing of Coding Sequences from GenomicDNA

[0290] Putative G-protein coupled receptors were initially identified byrunning the Genscan gene identification program against public genomicsequence databases (e.g., gbpri and gbhtg). Genscan is a general-purposegene identification program which analyzes genomic DNA sequences from avariety of organisms (See Burge, C. and S. Karlin (1997) J. Mol. Biol.268:78-94, and Burge, C. and S. Karlin (1998) Curr. Opin. Struct. Biol.8:346-354). The program concatenates predicted exons to form anassembled cDNA sequence extending from a methionine to a stop codon. Theoutput of Genscan is a FASTA database of polynucleotide and polypeptidesequences. The maximum range of sequence for Genscan to analyze at oncewas set to 30 kb. To determine which of these Genscan predicted cDNAsequences encode G-protein coupled receptors, the encoded polypeptideswere analyzed by querying against PFAM models for G-protein coupledreceptors. Potential G-protein coupled receptors were also identified byhomology to Incyte cDNA sequences that had been annotated as G-proteincoupled receptors. These selected Genscan-predicted sequences were thencompared by BLAST analysis to the genpept and gbpri public databases.Where necessary, the Genscan-predicted sequences were then edited bycomparison to the top BLAST hit from genpept to correct errors in thesequence predicted by Genscan, such as extra or omitted exons. BLASTanalysis was also used to find any Incyte cDNA or public cDNA coverageof the Genscan-predicted sequences, thus providing evidence fortranscription. When Incyte cDNA coverage was available, this informationwas used to correct or confirm the Genscan predicted sequence. Fulllength polynucleotide sequences were obtained by assemblingGenscan-predicted coding sequences with Incyte cDNA sequences and/orpublic cDNA sequences using the assembly process described in ExampleIII. Alternatively, full length polynucleotide sequences were derivedentirely from edited or unedited Genscan-predicted coding sequences.

[0291] V. Assembly of Genomic Sequence Data with cDNA Sequence Data

[0292] “Stitched” Sequences

[0293] Partial cDNA sequences were extended with exons predicted by theGenscan gene identification program described in Example IV. PartialcDNAs assembled as described in Example III were mapped to genomic DNAand parsed into clusters containing related cDNAs and Genscan exonpredictions from one or more genomic sequences. Each cluster wasanalyzed using an algorithm based on graph theory and dynamicprogramming to integrate cDNA and genomic information, generatingpossible splice variants that were subsequently confirmed, edited, orextended to create a full length sequence. Sequence intervals in whichthe entire length of the interval was present on more than one sequencein the cluster were identified, and intervals thus identified wereconsidered to be equivalent by transitivity. For example, if an intervalwas present on a cDNA and two genomic sequences, then all threeintervals were considered to be equivalent. This process allowsunrelated but consecutive genomic sequences to be brought together,bridged by cDNA sequence. Intervals thus identified were then “stitched”together by the stitching algorithm in the order that they appear alongtheir parent sequences to generate the longest possible sequence, aswell as sequence variants. Linkages between intervals which proceedalong one type of parent sequence (cDNA to cDNA or genomic sequence togenomic sequence) were given preference over linkages which changeparent type (cDNA to genomic sequence). The resultant stitched sequenceswere translated and compared by BLAST analysis to the genpept and gbpripublic databases. Incorrect exons predicted by Genscan were corrected bycomparison to the top BLAST hit from genpept. Sequences were furtherextended with additional cDNA sequences, or by inspection of genomicDNA, when necessary.

[0294] “Stretched” Sequences

[0295] Partial DNA sequences were extended to full length with analgorithm based on BLAST analysis. First, partial cDNAs assembled asdescribed in Example III were queried against public databases such asthe GenBank primate, rodent, mammalian, vertebrate, and eukaryotedatabases using the BLAST program. The nearest GenBank protein homologwas then compared by BLAST analysis to either Incyte cDNA sequences orGenScan exon predicted sequences described in Example IV. A chimericprotein was generated by using the resultant high-scoring segment pairs(HSPs) to map the translated sequences onto the GenBank protein homolog.Insertions or deletions may occur in the chimeric protein with respectto the original GenBank protein homolog. The GenBank protein homolog,the chimeric protein, or both were used as probes to search forhomologous genomic sequences from the public human genome databases.Partial DNA sequences were therefore “stretched” or extended by theaddition of homologous genomic sequences. The resultant stretchedsequences were examined to determine whether it contained a completegene.

[0296] VI. Chromosomal Mapping of GCREC Encoding Polynucleotides

[0297] The sequences which were used to assemble SEQ ID NO:49-96 werecompared with sequences from the Incyte LIFESEQ database and publicdomain databases using BLAST and other implementations of theSmith-Waterman algorithm. Sequences from these databases that matchedSEQ ID NO:49-96 were assembled into clusters of contiguous andoverlapping sequences using assembly algorithms such as Phrap (Table 7).Radiation hybrid and genetic mapping data available from publicresources such as the Stanford Human Genome Center (SHGC), WhiteheadInstitute for Genome Research (WIGR), and Généthon were used todetermine if any of the clustered sequences had been previously mapped.Inclusion of a mapped sequence in a cluster resulted in the assignmentof all sequences of that cluster, including its particular SEQ ID NO:,to that map location.

[0298] Map locations are represented by ranges, or intervals, of humanchromosomes. The map position of an interval, in centiMorgans, ismeasured relative to the terminus of the chromosome's p-arm. (ThecentiMorgan (cM) is a unit of measurement based on recombinationfrequencies between chromosomal markers. On average, 1 cM is roughlyequivalent to 1 megabase (Mb) of DNA in humans, although this can varywidely due to hot and cold spots of recombination.) The cM distances arebased on genetic markers mapped by Généthon which provide boundaries forradiation hybrid markers whose sequences were included in each of theclusters. Human genome maps and other resources available to the public,such as the NCBI “GeneMap”99” World Wide Web site(http://www.ncbi.nlm.nih.gov/genemap/), can be employed to determine ifpreviously identified disease genes map within or in proximity to theintervals indicated above.

[0299] VII. Analysis of Polynucleotide Expression

[0300] Northern analysis is a laboratory technique used to detect thepresence of a transcript of a gene and involves the hybridization of alabeled nucleotide sequence to a membrane on which RNAs from aparticular cell type or tissue have been bound. (See, e.g., Sambrook,supra, ch. 7; Ausubel (1995) supra, ch. 4 and 16.)

[0301] Analogous computer techniques applying BLAST were used to searchfor identical or related molecules in cDNA databases such as GenBank orLIFESEQ (Incyte Genomics). This analysis is much faster than multiplemembrane-based hybridizations. In addition, the sensitivity of thecomputer search can be modified to determine whether any particularmatch is categorized as exact or similar. The basis of the search is theproduct score, which is defined as:

BLAST Score×Percent Identity/5× minimum {length(Seq. 1), length(Seq. 2)}

[0302] The product score takes into account both the degree ofsimilarity between two sequences and the length of the sequence match.The product score is a normalized value between 0 and 100, and iscalculated as follows: the BLAST score is multiplied by the percentnucleotide identity and the product is divided by (5 times the length ofthe shorter of the two sequences). The BLAST score is calculated byassigning a score of +5 for every base that matches in a high-scoringsegment pair (HSP), and −4 for every mismatch. Two sequences may sharemore than one HSP (separated by gaps). If there is more than one HSP,then the pair with the highest BLAST score is used to calculate theproduct score. The product score represents a balance between fractionaloverlap and quality in a BLAST alignment. For example, a product scoreof 100 is produced only for 100% identity over the entire length of theshorter of the two sequences being compared. A product score of 70 isproduced either by 100% identity and 70% overlap at one end, or by 88%identity and 100% overlap at the other. A product score of 50 isproduced either by 100% identity and 50% overlap at one end, or 79%identity and 100% overlap.

[0303] Alternatively, polynucleotide sequences encoding GCREC areanalyzed with respect to the tissue sources from which they werederived. For example, some full length sequences are assembled, at leastin part, with overlapping Incyte cDNA sequences (see Example III). EachcDNA sequence is derived from a cDNA library constructed from a humantissue. Each human tissue is classified into one of the followingorgan/tissue categories: cardiovascular system; connective tissue;digestive system; embryonic structures; endocrine system; exocrineglands; genitalia, female; genitalia, male; germ cells; hemic and immunesystem; liver; musculoskeletal system; nervous system; pancreas;respiratory system; sense organs; skin; stomatognathic system;unclassified/mixed; or urinary tract. The number of libraries in eachcategory is counted and divided by the total number of libraries acrossall categories. Similarly, each human tissue is classified into one ofthe following disease/condition categories: cancer, cell line,developmental, inflammation, neurological, trauma, cardiovascular,pooled, and other, and the number of libraries in each category iscounted and divided by the total number of libraries across allcategories. The resulting percentages reflect the tissue- anddisease-specific expression of cDNA encoding GCREC. cDNA sequences andcDNA library/tissue information are found in the LIFESEQ GOLD database(Incyte Genomics, Palo Alto Calif.).

[0304] VIII. Extension of GCREC Encoding Polynucleotides

[0305] Full length polynucleotide sequences were also produced byextension of an appropriate fragment of the full length molecule usingoligonucleotide primers designed from this fragment. One primer wassynthesized to initiate 5′ extension of the known fragment, and theother primer was synthesized to initiate 3′ extension of the knownfragment. The initial primers were designed using OLIGO 4.06 software(National Biosciences), or another appropriate program, to be about 22to 30 nucleotides in length, to have a GC content of about 50% or more,and to anneal to the target sequence at temperatures of about 68° C. toabout 72° C. Any stretch of nucleotides which would result in hairpinstructures and primer-primer dimerizations was avoided.

[0306] Selected human cDNA libraries were used to extend the sequence.If more than one extension was necessary or desired, additional ornested sets of primers were designed.

[0307] High fidelity amplification was obtained by PCR using methodswell known in the art. PCR was performed in 96-well plates using thePTC-200 thermal cycler (MJ Research, Inc.). The reaction mix containedDNA template, 200 nmol of each primer, reaction buffer containing Mg²⁺,(NH₄)₂SO₄, and 2-mercaptoethanol, Taq DNA polymerase (Amersham PharmaciaBiotech), ELONGASE enzyme (Life Technologies), and Pfu DNA polymerase(Stratagene), with the following parameters for primer pair PCI A andPCI B: Step 1: 94° C., 3 min; Step 2: 94° C., 15 sec; Step 3: 60° C., 1min Step 4: 68° C., 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times;Step 6: 68° C., 5 min; Step 7: storage at 4° C. In the alternative, theparameters for primer pair T7 and SK+ were as follows: Step 1: 94° C., 3min; Step 2: 94° C., 15 sec; Step 3: 57° C., 1 min; Step 4: 68° C., 2min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68° C., 5 min;Step 7: storage at 4° C.

[0308] The concentration of DNA in each well was determined bydispensing 100 μl PICOGREEN quantitation reagent (0.25% (v/v) PICOGREEN;Molecular Probes, Eugene Oreg.) dissolved in 1X TE and 0.5 μl ofundiluted PCR product into each well of an opaque fluorimeter plate(Corning Costar, Acton Mass.), allowing the DNA to bind to the reagent.The plate was scanned in a Fluoroskan II (Labsystems Oy, Helsinki,Finland) to measure the fluorescence of the sample and to quantify theconcentration of DNA. A 5 μl to 10 μl aliquot of the reaction mixturewas analyzed by electrophoresis on a 1% agarose gel to determine whichreactions were successful in extending the sequence.

[0309] The extended nucleotides were desalted and concentrated,transferred to 384-well plates, digested with CviJI cholera virusendonuclease (Molecular Biology Research, Madison Wis.), and sonicatedor sheared prior to religation into pUC 18 vector (Amersham PharmaciaBiotech). For shotgun sequencing, the digested nucleotides wereseparated on low concentration (0.6 to 0.8%) agarose gels, fragmentswere excised, and agar digested with Agar ACE (Promega). Extended cloneswere religated using T4 ligase (New England Biolabs, Beverly Mass.) intopUC 18 vector (Amersham Pharmacia Biotech), treated with Pfu DNApolymerase (Stratagene) to fill-in restriction site overhangs, andtransfected into competent E. coli cells. Transformed cells wereselected on antibiotic-containing media, and individual colonies werepicked and cultured overnight at 37° C. in 384-well plates in LB/2× carbliquid media.

[0310] The cells were lysed, and DNA was amplified by PCR using Taq DNApolymerase (Amersham Pharmacia Biotech) and Pfu DNA polymerase(Stratagene) with the following parameters: Step 1: 94° C., 3 min; Step2: 94° C., 15 sec; Step 3: 60° C., 1 min; Step 4: 72° C., 2 min; Step 5:steps 2, 3, and 4 repeated 29 times; Step 6: 72° C., 5 min; Step 7:storage at 4° C. DNA was quantified by PICOGREEN reagent (MolecularProbes) as described above. Samples with low DNA recoveries werereamplified using the same conditions as described above. Samples werediluted with 20% dimethysulfoxide (1:2, v/v), and sequenced usingDYENAMIC energy transfer sequencing primers and the DYENAMIC DIRECT kit(Amersham Pharmacia Biotech) or the ABI PRISM BIGDYE Terminator cyclesequencing ready reaction kit (Applied Biosystems).

[0311] In like manner, full length polynucleotide sequences are verifiedusing the above procedure or are used to obtain 5′ regulatory sequencesusing the above procedure along with oligonucleotides designed for suchextension, and an appropriate genomic library.

[0312] IX. Identification of Single Nucleotide Polymorphisms in GCRECEncoding Polynucleotides

[0313] Common DNA sequence variants known as single nucleotidepolymorphisms (SNPs) were identified in SEQ ID NO:49-96 using theLIFESEQ database (Incyte Genomics). Sequences from the same gene wereclustered together and assembled as described in Example III, allowingthe identification of all sequence variants in the gene. An algorithmconsisting of a series of filters was used to distinguish SNPs fromother sequence variants. Preliminary filters removed the majority ofbasecall errors by requiring a minimum Phred quality score of 15, andremoved sequence alignment errors and errors resulting from impropertrimming of vector sequences, chimeras, and splice variants. Anautomated procedure of advanced chromosome analysis analysed theoriginal chromatogram files in the vicinity of the putative SNP. Cloneerror filters used statistically generated algorithms to identify errorsintroduced during laboratory processing, such as those caused by reversetranscriptase, polymerase, or somatic mutation. Clustering error filtersused statistically generated algorithms to identify errors resultingfrom clustering, of close homologs or pseudogenes, or due tocontamination by non-human sequences. A final set of filters removedduplicates and SNPs found in immunoglobulins or T-cell receptors.

[0314] Certain SNPs were selected for further characterization by massspectrometry using the high throughput MASSARRAY system (Sequenom, Inc.)to analyze allele frequencies at the SNP sites in four different humanpopulations. The Caucasian population comprised 92 individuals (46 male,46 female), including 83 from Utah, four French, three Venezualan, andtwo Amish individuals. The African population comprised 194 individuals(97 male, 97 female), all African Americans. The Hispanic populationcomprised 324 individuals (162 male, 162 female), all Mexican Hispanic.The Asian population comprised 126 individuals (64 male, 62 female) witha reported parental breakdown of 43% Chinese, 31% Japanese, 13% Korean,5% Vietnamese, and 8% other Asian. Allele frequencies were firstanalyzed in the Caucasian population; in some cases those SNPs whichshowed no allelic variance in this population were not further tested inthe other three populations.

[0315] X. Labeling and Use of Individual Hybridization Probes

[0316] Hybridization probes derived from SEQ ID NO:49-96 are employed toscreen cDNAs, genomic DNAs, or mRNAs. Although the labeling ofoligonucleotides, consisting of about 20 base pairs, is specificallydescribed, essentially the same procedure is used with larger nucleotidefragments. Oligonucleotides are designed using state-of-the-art softwaresuch as OLIGO 4.06 software (National Biosciences) and labeled bycombining 50 pmol of each oligomer, 250 μCi of [γ-³²P] adenosinetriphosphate (Amersham Pharmacia Biotech), and T4 polynucleotide kinase(DuPont NEN, Boston Mass.). The labeled oligonucleotides aresubstantially purified using a SEPHADEX G-25 superfine size exclusiondextran bead column (Amersham Pharmacia Biotech). An aliquot containing10⁷ counts per minute of the labeled probe is used in a typicalmembrane-based hybridization analysis of human genomic DNA digested withone of the following endonucleases: Ase I, Bgl II, Eco RI, Pst I, Xba I,or Pvu II (DuPont NEN).

[0317] The DNA from each digest is fractionated on a 0.7% agarose geland transferred to nylon membranes (Nytran Plus, Schleicher & Schuell,Durham N.H.). Hybridization is carried out for 16 hours at 40° C. Toremove nonspecific signals, blots are sequentially washed at roomtemperature under conditions of up to, for example, 0.1× saline sodiumcitrate and 0.5% sodium dodecyl sulfate. Hybridization patterns arevisualized using autoradiography or an alternative imaging means andcompared.

[0318] XI. Microarrays

[0319] The linkage or synthesis of array elements upon a microarray canbe achieved utilizing photolithography, piezoelectric printing (ink-jetprinting, See, e.g., Baldeschweiler, supra.), mechanical microspottingtechnologies, and derivatives thereof. The substrate in each of theaforementioned technologies should be uniform and solid with anon-porous surface (Schena (1999), supra). Suggested substrates includesilicon, silica, glass slides, glass chips, and silicon wafers.Alternatively, a procedure analogous to a dot or slot blot may also beused to arrange and link elements to the surface of a substrate usingthermal, UV, chemical, or mechanical bonding procedures. A typical arraymay be produced using available methods and machines well known to thoseof ordinary skill in the art and may contain any appropriate number ofelements. (See, e.g., Schena, M. et al. (1995) Science 270:467-470;Shalon, D. et al. (1996) Genome Res. 6:639-645; Marshall, A. and J.Hodgson (1998) Nat. Biotechnol. 16:27-31.)

[0320] Full length cDNAs, Expressed Sequence Tags (ESTs), or fragmentsor oligomers thereof may comprise the elements of the microarray.Fragments or oligomers suitable for hybridization can be selected usingsoftware well known in the art such as LASERGENE software (DNASTAR). Thearray elements are hybridized with polynucleotides in a biologicalsample. The polynucleotides in the biological sample are conjugated to afluorescent label or other molecular tag for ease of detection. Afterhybridization, nonhybridized nucleotides from the biological sample areremoved, and a fluorescence scanner is used to detect hybridization ateach array element. Alternatively, laser desorbtion and massspectrometry may be used for detection of hybridization. The degree ofcomplementarity and the relative abundance of each polynucleotide whichhybridizes to an element on the microarray may be assessed. In oneembodiment, microarray preparation and usage is described in detailbelow.

[0321] Tissue or Cell Sample Preparation

[0322] Total RNA is isolated from tissue samples using the guanidiniumthiocyanate method and poly(A)⁺ RNA is purified using the oligo-(dT)cellulose method. Each poly(A)⁺ RNA sample is reverse transcribed usingMMLV reverse-transcriptase, 0.05 pg/μl oligo-(dT) primer (21 mer), 1Xfirst strand buffer, 0.03 units/μl RNase inhibitor, 500 μM dATP, 500 μMdGTP, 500 μM dTTP, 40 μM dCTP, 40 μM dCTP-Cy3 (BDS) or dCTP-Cy5(Amersham Pharmacia Biotech). The reverse transcription reaction isperformed in a 25 ml volume containing 200 ng poly(A)⁺ RNA withGEMBRIGHT kits (Incyte). Specific control poly(A)⁺ RNAs are synthesizedby in vitro transcription from non-coding yeast genomic DNA. Afterincubation at 37° C. for 2 hr, each reaction sample (one with Cy3 andanother with Cy5 labeling) is treated with 2.5 ml of 0.5M sodiumhydroxide and incubated for 20 minutes at 85° C. to the stop thereaction and degrade the RNA. Samples are purified using two successiveCHROMA SPIN 30 gel filtration spin columns (CLONTECH Laboratories, Inc.(CLONTECH), Palo Alto Calif.) and after combining, both reaction samplesare ethanol precipitated using 1 ml of glycogen (1 mg/ml), 60 ml sodiumacetate, and 300 ml of 100% ethanol. The sample is then dried tocompletion using a SpeedVAC (Savant Instruments Inc., Holbrook N.Y.) andresuspended in 14 μl 5×SSC/0.2% SDS.

[0323] Microarray Preparation

[0324] Sequences of the present invention are used to generate arrayelements. Each array element is amplified from bacterial cellscontaining vectors with cloned cDNA inserts. PCR amplification usesprimers complementary to the vector sequences flanking the cDNA insert.Array elements are amplified in thirty cycles of PCR from an initialquantity of 1-2 ng to a final quantity greater than 5 μg. Amplifiedarray elements are then purified using SEPHACRYL-400 (Amersham PharmaciaBiotech).

[0325] Purified array elements are immobilized on polymer-coated glassslides. Glass microscope slides (Corning) are cleaned by ultrasound in0.1% SDS and acetone, with extensive distilled water washes between andafter treatments. Glass slides are etched in 4% hydrofluoric acid (VWRScientific Products Corporation (VWR), West Chester Pa.), washedextensively in distilled water, and coated with 0.05% aminopropyl silane(Sigma) in 95% ethanol. Coated slides are cured in a 110° C. oven.

[0326] Array elements are applied to the coated glass substrate using aprocedure described in U.S. Pat. No. 5,807,522, incorporated herein byreference. 1 μl of the array element DNA, at an average concentration of100 ng/μl, is loaded into the open capillary printing element by ahigh-speed robotic apparatus. The apparatus then deposits about 5 nl ofarray element sample per slide.

[0327] Microarrays are UV-crosslinked using a STRATALINKERUV-crosslinker (Stratagene). Microarrays are washed at room temperatureonce in 0.2% SDS and three times in distilled water. Non-specificbinding sites are blocked by incubation of microarrays in 0.2% casein inphosphate buffered saline (PBS) (Tropix, Inc., Bedford Mass.) for 30minutes at 60° C. followed by washes in 0.2% SDS and distilled water asbefore.

[0328] Hybridization

[0329] Hybridization reactions contain 9 μl of sample mixture consistingof 0.2 μg each of Cy3 and Cy5 labeled cDNA synthesis products in 5×SSC,0.2% SDS hybridization buffer. The sample mixture is heated to 65° C.for 5 minutes and is aliquoted onto the microarray surface and coveredwith an 1.8 cm² coverslip. The arrays are transferred to a waterproofchamber having a cavity just slightly larger than a microscope slide.The chamber is kept at 100% humidity internally by the addition of 140μl of 5×SSC in a corner of the chamber. The chamber containing thearrays is incubated for about 6.5 hours at 60° C. The arrays are washedfor 10 min at 45° C. in a first wash buffer (1×SSC, 0.1% SDS), threetimes for 10 minutes each at 45° C. in a second wash buffer (0.1×SSC),and dried.

[0330] Detection

[0331] Reporter-labeled hybridization complexes are detected with amicroscope equipped with an Innova 70 mixed gas 10 W laser (Coherent,Inc., Santa Clara Calif.) capable of generating spectral lines at 488 nmfor excitation of Cy3 and at 632 nm for excitation of Cy5. Theexcitation laser light is focused on the array using a 20× microscopeobjective (Nikon, Inc., Melville N.Y.). The slide containing the arrayis placed on a computer-controlled X-Y stage on the microscope andraster-scanned past the objective. The 1.8 cm×1.8 cm array used in thepresent example is scanned with a resolution of 20 micrometers.

[0332] In two separate scans, a mixed gas multiline laser excites thetwo fluorophores sequentially. Emitted light is split, based onwavelength, into two photomultiplier tube detectors (PMT R1477,Hamamatsu Photonics Systems, Bridgewater N.J.) corresponding to the twofluorophores. Appropriate filters positioned between the array and thephotomultiplier tubes are used to filter the signals. The emissionmaxima of the fluorophores used are 565 nm for Cy3 and 650 nm for Cy5.Each array is typically scanned twice, one scan per fluorophore usingthe appropriate filters at the laser source, although the apparatus iscapable of recording the spectra from both fluorophores simultaneously.

[0333] The sensitivity of the scans is typically calibrated using thesignal intensity generated by a cDNA control species added to the samplemixture at a known concentration. A specific location on the arraycontains a complementary DNA sequence, allowing the intensity of thesignal at that location to be correlated with a weight ratio ofhybridizing species of 1:100,000. When two samples from differentsources (e.g., representing test and control cells), each labeled with adifferent fluorophore, are hybridized to a single array for the purposeof identifying genes that are differentially expressed, the calibrationis done by labeling samples of the calibrating cDNA with the twofluorophores and adding identical amounts of each to the hybridizationmixture.

[0334] The output of the photomultiplier tube is digitized using a12-bit RTI-835H analog-to-digital (A/D) conversion board (AnalogDevices, Inc., Norwood Mass.) installed in an IBM-compatible PCcomputer. The digitized data are displayed as an image where the signalintensity is mapped using a linear 20-color transformation to apseudocolor scale ranging from blue (low signal) to red (high signal).The data is also analyzed quantitatively. Where two differentfluorophores are excited and measured simultaneously, the data are firstcorrected for optical crosstalk (due to overlapping emission spectra)between the fluorophores using each fluorophore's emission spectrum.

[0335] A grid is superimposed over the fluorescence signal image suchthat the signal from each spot is centered in each element of the grid.The fluorescence signal within each element is then integrated to obtaina numerical value corresponding to the average intensity of the signal.The software used for signal analysis is the GEMTOOLS gene expressionanalysis program (Incyte).

[0336] Expression

[0337] For example, for component 2112194 of SEQ ID NO:64, peripheralblood cells (PBMCs) are collected from the blood of 6 donors usingstandard gradient separation. The PBMCs from each donor are placed inculture for 2 hours in the presence or absence of recombinantinterleukin-5 (IL-5). IL-5 treated PBMCs and untreated control PBMCsfrom the different donors are pooled according to their respectivetreatments. In this manner, it was demonstrated that treatment with IL-5alters the expression of component 2112194 of SEQ ID NO:64 in PBMCs by afactor of at least 2.

[0338] Alternatively, for component 2112194 of SEQ ID NO:64, a normalhuman mammary epithelial cell (HMEC) population is compared to breastcarcinoma lines at various stages of tumor progression. Samples arelysed in Trizol and the total RNA fraction is recovered. Poly-A mRNA ispurified using a standard oligo-dT selection method. Gene expressionprofiles of HMEC cells are compared to those of the breast carcinomalines. In this manner, it was demonstrated that the expression ofcomponent 2112194 of SEQ ID NO:64 is altered by a factor of at least 2during breast tumor progression.

[0339] XII. Complementary Polynucleotides

[0340] Sequences complementary to the GCREC-encoding sequences, or anyparts thereof, are used to detect, decrease, or inhibit expression ofnaturally occurring GCREC. Although use of oligonucleotides comprisingfrom about 15 to 30 base pairs is described, essentially the sameprocedure is used with smaller or with larger sequence fragments.Appropriate oligonucleotides are designed using OLIGO 4.06 software(National Biosciences) and the coding sequence of GCREC. To inhibittranscription, a complementary oligonucleotide is designed from the mostunique 5′ sequence and used to prevent promoter binding to the codingsequence. To inhibit translation, a complementary oligonucleotide isdesigned to prevent ribosomal binding to the GCREC-encoding transcript.

[0341] XIII. Expression of GCREC

[0342] Expression and purification of GCREC is achieved using bacterialor virus-based expression systems. For expression of GCREC in bacteria,cDNA is subcloned into an appropriate vector containing an antibioticresistance gene and an inducible promoter that directs high levels ofcDNA transcription. Examples of such promoters include, but are notlimited to, the trp-lac (tac) hybrid promoter and the T5 or T7bacteriophage promoter in conjunction with the lac operator regulatoryelement. Recombinant vectors are transformed into suitable bacterialhosts, e.g., BL21(DE3). Antibiotic resistant bacteria express GCREC uponinduction with isopropyl beta-D-thiogalactopyranoside (IPTG). Expressionof GCREC in eukaryotic cells is achieved by infecting insect ormammalian cell lines with recombinant Autographica californica nuclearpolyhedrosis virus (AcMNPV), commonly known as baculovirus. Thenonessential polyhedrin gene of baculovirus is replaced with cDNAencoding GCREC by either homologous recombination or bacterial-mediatedtransposition involving transfer plasmid intermediates. Viralinfectivity is maintained and the strong polyhedrin promoter drives highlevels of cDNA transcription. Recombinant baculovirus is used to infectSpodoptera frugiperda (Sf9) insect cells in most cases, or humanhepatocytes, in some cases. Infection of the latter requires additionalgenetic modifications to baculovirus. (See Engelhard, E. K. et al.(1994) Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996)Hum. Gene Ther. 7:1937-1945.)

[0343] In most expression systems, GCREC is synthesized as a fusionprotein with, e.g., glutathione S-transferase (GST) or a peptide epitopetag, such as FLAG or 6-His, permitting rapid, single-step,affinity-based purification of recombinant fusion protein from crudecell lysates. GST, a 26-kilodalton enzyme from Schistosoma japonicum,enables the purification of fusion proteins on immobilized glutathioneunder conditions that maintain protein activity and antigenicity(Amersham Pharmacia Biotech). Following purification, the GST moiety canbe proteolytically cleaved from GCREC at specifically engineered sites.FLAG, an 8-amino acid peptide, enables immunoaffinity purification usingcommercially available monoclonal and polyclonal anti-FLAG antibodies(Eastman Kodak). 6-His, a stretch of six consecutive histidine residues,enables purification on metal-chelate resins (QIAGEN). Methods forprotein expression and purification are discussed in Ausubel (1995,supra, ch. 10 and 16). Purified GCREC obtained by these methods can beused directly in the assays shown in Examples XVII, XVIII, and XIX,where applicable.

[0344] XIV. Functional Assays

[0345] GCREC function is assessed by expressing the sequences encodingGCREC at physiologically elevated levels in mammalian cell culturesystems. cDNA is subcloned into a mammalian expression vector containinga strong promoter that drives high levels of cDNA expression. Vectors ofchoice include PCMV SPORT (Life Technologies) and PCR3.1 (Invitrogen,Carlsbad Calif.), both of which contain the cytomegalovirus promoter.5-10 μg of recombinant vector are transiently transfected into a humancell line, for example, an endothelial or hematopoietic cell line, usingeither liposome formulations or electroporation. 1-2 μg of an additionalplasmid containing sequences encoding a marker protein areco-transfected. Expression of a marker protein provides a means todistinguish transfected cells from nontransfected cells and is areliable predictor of cDNA expression from the recombinant vector.Marker proteins of choice include, e.g., Green Fluorescent Protein (GFP;Clontech), CD64, or a CD64-GFP fusion protein. Flow cytometry (FCM), anautomated, laser optics-based technique, is used to identify transfectedcells expressing GFP or CD64-GFP and to evaluate the apoptotic state ofthe cells and other cellular properties. FCM detects and quantifies theuptake of fluorescent molecules that diagnose events preceding orcoincident with cell death. These events include changes in nuclear DNAcontent as measured by staining of DNA with propidium iodide; changes incell size and granularity as measured by forward light scatter and 90degree side light scatter; down-regulation of DNA synthesis as measuredby decrease in bromodeoxyuridine uptake; alterations in expression ofcell surface and intracellular proteins as measured by reactivity withspecific antibodies; and alterations in plasma membrane composition asmeasured by the binding of fluorescein-conjugated Annexin V protein tothe cell surface. Methods in flow cytometry are discussed in Ormerod, M.G. (1994) Flow Cytometry, Oxford, New York N.Y.

[0346] The influence of GCREC on gene expression can be assessed usinghighly purified populations of cells transfected with sequences encodingGCREC and either CD64 or CD64-GFP. CD64 and CD64-GFP are expressed onthe surface of transfected cells and bind to conserved regions of humanimmunoglobulin G (IgG). Transfected cells are efficiently separated fromnontransfected cells using magnetic beads coated with either human IgGor antibody against CD64 (DYNAL, Lake Success N.Y.). mRNA can bepurified from the cells using methods well known by those of skill inthe art. Expression of mRNA encoding GCREC and other genes of interestcan be analyzed by northern analysis or microarray techniques.

[0347] XV. Production of GCREC Specific Antibodies

[0348] GCREC substantially purified using polyacrylamide gelelectrophoresis (PAGE; see, e.g., Harrington, M. G. (1990) MethodsEnzymol. 182:488-495), or other purification techniques, is used toimmunize animals (e.g., rabbits, mice, etc.) and to produce antibodiesusing standard protocols.

[0349] Alternatively, the GCREC amino acid sequence is analyzed usingLASERGENE software (DNASTAR) to determine regions of highimmunogenicity, and a corresponding oligopeptide is synthesized and usedto raise antibodies by means known to those of skill in the art. Methodsfor selection of appropriate epitopes, such as those near the C-terminusor in hydrophilic regions are well described in the art. (See, e.g.,Ausubel, 1995, supra, ch. 11.)

[0350] Typically, oligopeptides of about 15 residues in length aresynthesized using an ABI 431A peptide synthesizer (Applied Biosystems)using FMOC chemistry and coupled to KLH (Sigma-Aldrich, St. Louis Mo.)by reaction with N-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) toincrease immunogenicity. (See, e.g., Ausubel, 1995, supra.) Rabbits areimmunized with the oligopeptide-KLH complex in complete Freund'sadjuvant. Resulting antisera are tested for antipeptide and anti-GCRECactivity by, for example, binding the peptide or GCREC to a substrate,blocking with 1% BSA, reacting with rabbit antisera, washing, andreacting with radio-iodinated goat anti-rabbit IgG.

[0351] XVI. Purification of Naturally Occurring GCREC Using SpecificAntibodies

[0352] Naturally occurring or recombinant GCREC is substantiallypurified by immunoaffinity chromatography using antibodies specific forGCREC. An immunoaffinity column is constructed by covalently couplinganti-GCREC antibody to an activated chromatographic resin, such asCNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After thecoupling, the resin is blocked and washed according to themanufacturer's instructions.

[0353] Media containing GCREC are passed over the immunoaffinity column,and the column is washed under conditions that allow the preferentialabsorbance of GCREC (e.g., high ionic strength buffers in the presenceof detergent). The column is eluted under conditions that disruptantibody/GCREC binding (e.g., a buffer of pH 2 to pH 3, or a highconcentration of a chaotrope, such as urea or thiocyanate ion), andGCREC is collected.

[0354] XVII. Identification of Molecules Which Interact with GCREC

[0355] Molecules which interact with GCREC may include agonists andantagonists, as well as molecules involved in signal transduction, suchas G proteins. GCREC, or a fragment thereof, is labeled with ¹²⁵IBolton-Hunter reagent. (See, e.g., Bolton A. E. and W. M. Hunter (1973)Biochem. J. 133:529-539.) A fragment of GCREC includes, for example, afragment comprising one or more of the three extracellular loops, theextracellular N-terminal region, or the third intracellular loop.Candidate molecules previously arrayed in the wells of a multi-wellplate are incubated with the labeled GCREC, washed, and any wells withlabeled GCREC complex are assayed. Data obtained using differentconcentrations of GCREC are used to calculate values for the number,affinity, and association of GCREC with the candidate ligand molecules.

[0356] Alternatively, molecules interacting with GCREC are analyzedusing the yeast two-hybrid system as described in Fields, S. and O. Song(1989) Nature 340:245-246, or using commercially available kits based onthe two-hybrid system, such as the MATCHMAKER system (Clontech). GCRECmay also be used in the PATHCALLING process (CuraGen Corp., New HavenConn.) which employs the yeast two-hybrid system in a high-throughputmanner to determine all interactions between the proteins encoded by twolarge libraries of genes (Nandabalan, K. et al. (2000) U.S. Pat. No.6,057,101).

[0357] Potential GCREC agonists or antagonists may be tested foractivation or inhibition of GCREC receptor activity using the assaysdescribed in sections XVII and XVIII. Candidate molecules may beselected from known GPCR agonists or antagonists, peptide libraries, orcombinatorial chemical libraries.

[0358] Methods for detecting interactions of GCREC with intracellularsignal transduction molecules such as G proteins are based on thepremise that internal segments or cytoplasmic domains from an orphan Gprotein-coupled seven transmembrane receptor may be exchanged with theanalogous domains of a known G protein-coupled seven transmembranereceptor and used to identify the G-proteins and downstream signalingpathways activated by the orphan receptor domains (Kobilka, B. K. et al.(1988) Science 240:1310-1316). In an analogous fashion, domains of theorphan receptor may be cloned as a portion of a fusion protein and usedin binding assays to demonstrate interactions with specific G proteins.Studies have shown that the third intracellular loop of Gprotein-coupled seven transmembrane receptors is important for G proteininteraction and signal transduction (Conklin, B. R. et al. (1993) Cell73:631-641). For example, the DNA fragment corresponding to the thirdintracellular loop of GCREC may be amplified by the polymerase chainreaction (PCR) and subcloned into a fusion vector such as pGEX(Pharmacia Biotech). The construct is transformed into an appropriatebacterial host, induced, and the fusion protein is purified from thecell lysate by glutathione-Sepharose 4B (Pharmacia Biotech) affinitychromatography.

[0359] For in vitro binding assays, cell extracts containing G proteinsare prepared by extraction with 50 mM Tris, pH 7.8, 1 mM EGTA, 5 mMMgCl₂, 20 mM CHAPS, 20% glycerol, 10 μg of both aprotinin and leupeptin,and 20 μl of 50 mM phenylmethylsulfonyl fluoride. The lysate isincubated on ice for 45 min with constant stirring, centrifuged at23,000 g for 15 min at 4° C., and the supernatant is collected. 750 μgof cell extract is incubated with glutathione S-transferase (GST) fusionprotein beads for 2 h at 4° C. The GST beads are washed five times withphosphate-buffered saline. Bound G protein subunits are detected by[³²P]ADP-ribosylation with pertussis or cholera toxins. The reactionsare terminated by the addition of SDS sample buffer (4.6% (w/v) SDS, 10%(v/v) β-mercaptoethanol, 20% (w/v) glycerol, 95.2 mM Tris-HCl, pH 6.8,0.01% (w/v) bromphenol blue). The [³²P]ADP-labeled proteins areseparated on 10% SDS-PAGE gels, and autoradiographed. The separatedproteins in these gels are transferred to nitrocellulose paper, blockedwith blotto (5% nonfat dried milk, 50 mM Tris-HCl (pH 8.0), 2 mM CaCl₂,80 mM NaCl, 0.02% NaN₃, and 0.2% Nonidet P-40) for 1 hour at roomtemperature, followed by incubation for 1.5 hours with Gα subtypeselective antibodies (1:500; Calbiochem-Novabiochem). After threewashes, blots are incubated with horseradish peroxidase (HRP)-conjugatedgoat anti-rabbit immunoglobulin (1:2000, Cappel, Westchester Pa.) andvisualized by the chemiluminescence-based ECL method (Amersham Corp.).

[0360] XVIII. Demonstration of GCREC Activity

[0361] An assay for GCREC activity measures the expression of GCREC onthe cell surface. cDNA encoding GCREC is transfected into an appropriatemammalian cell line. Cell surface proteins are labeled with biotin asdescribed (de la Fuente, M. A. et al. (1997) Blood 90:2398-2405).Immunoprecipitations are performed using GCREC-specific antibodies, andimmunoprecipitated samples are analyzed using sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE) and immunoblottingtechniques. The ratio of labeled immunoprecipitant to unlabeledimmunoprecipitant is proportional to the amount of GCREC expressed onthe cell surface.

[0362] In the alternative, an assay for GCREC activity is based on aprototypical assay for ligand/receptor-mediated modulation of cellproliferation. This assay measures the rate of DNA synthesis in Swissmouse 3T3 cells. A plasmid containing polynucleotides encoding GCREC isadded to quiescent 3T3 cultured cells using transfection methods wellknown in the art. The transiently transfected cells are then incubatedin the presence of [³H]thymidine, a radioactive DNA precursor molecule.Varying amounts of GCREC ligand are then added to the cultured cells.Incorporation of (³H]thymidine into acid-precipitable DNA is measuredover an appropriate time interval using a radioisotope counter, and theamount incorporated is directly proportional to the amount of newlysynthesized DNA. A linear dose-response curve over at least ahundred-fold GCREC ligand concentration range is indicative of receptoractivity. One unit of activity per milliliter is defined as theconcentration of GCREC producing a 50% response level, where 100%represents maximal incorporation of [³H]thymidine into acid-precipitableDNA (McKay, I. and I. Leigh, eds. (1993) Growth Factors: A PracticalApproach, Oxford University Press, New York N.Y., p. 73.)

[0363] In a further alternative, the assay for GCREC activity is basedupon the ability of GPCR family proteins to modulate G protein-activatedsecond messenger signal transduction pathways (e.g., cAMP; Gaudin, P. etal. (1998) J. Biol. Chem. 273:4990-4996). A plasmid encoding full lengthGCREC is transfected into a mammalian cell line (e.g., Chinese hamsterovary (CHO) or human embryonic kidney (HEK-293) cell lines) usingmethods well-known in the art. Transfected cells are grown in 12-welltrays in culture medium for 48 hours, then the culture medium isdiscarded, and the attached cells are gently washed with PBS. The cellsare then incubated in culture medium with or without ligand for 30minutes, then the medium is removed and cells lysed by treatment with 1M perchloric acid. The cAMP levels in the lysate are measured byradioimmunoassay using methods well-known in the art. Changes in thelevels of cAMP in the lysate from cells exposed to ligand compared tothose without ligand are proportional to the amount of GCREC present inthe transfected cells.

[0364] To measure changes in inositol phosphate levels, the cells aregrown in 24-well plates containing 1×10⁵ cells/well and incubated withinositol-free media and [³H]myoinositol, 2 μCi/well, for 48 hr. Theculture medium is removed, and the cells washed with buffer containing10 mM LiCl followed by addition of ligand. The reaction is stopped byaddition of perchloric acid. Inositol phosphates are extracted andseparated on Dowex AG1-X8 (Bio-Rad) anion exchange resin, and the totallabeled inositol phosphates counted by liquid scintillation. Changes inthe levels of labeled inositol phosphate from cells exposed to ligandcompared to those without ligand are proportional to the amount of GCRECpresent in the transfected cells.

[0365] XIX. Identification of GCREC Ligands

[0366] GCREC is expressed in a eukaryotic cell line such as CHO (ChineseHamster Ovary) or HEK (Human Embryonic Kidney) 293 which have a goodhistory of GPCR expression and which contain a wide range of G-proteinsallowing for functional coupling of the expressed GCREC to downstreameffectors. The transformed cells are assayed for activation of theexpressed receptors in the presence of candidate ligands. Activity ismeasured by changes in intracellular second messengers, such as cyclicAMP or Ca²⁺. These may be measured directly using standard methods wellknown in the art, or by the use of reporter gene assays in which aluminescent protein (e.g. firefly luciferase or green fluorescentprotein) is under the transcriptional control of a promoter responsiveto the stimulation of protein kinase C by the activated receptor(Milligan, G. et al. (1996) Trends Pharmacol. Sci. 17:235-237). Assaytechnologies are available for both of these second messenger systems toallow high throughput readout in multi-well plate format, such as theadenylyl cyclase activation FlashPlate Assay (NEN Life SciencesProducts), or fluorescent Ca²⁺ indicators such as Fluo-4 AM (MolecularProbes) in combination with the FLIPR fluorimetric plate reading system(Molecular Devices). In cases where the physiologically relevant secondmessenger pathway is not known, GCREC may be coexpressed with theG-proteins G_(α15/16) which have been demonstrated to couple to a widerange of G-proteins (Offermanns, S. and M. I. Simon (1995) J. Biol.Chem. 270:15175-15180), in order to funnel the signal transduction ofthe GCREC through a pathway involving phospholipase C and Ca²⁺mobilization. Alternatively, GCREC may be expressed in engineered yeastsystems which lack endogenous GPCRs, thus providing the advantage of anull background for GCREC activation screening. These yeast systemssubstitute a human GPCR and G_(α) protein for the correspondingcomponents of the endogenous yeast pheromone receptor pathway.Downstream signaling pathways are also modified so that the normal yeastresponse to the signal is converted to positive growth on selectivemedia or to reporter gene expression (Broach, J. R. and J. Thorner(1996) Nature 384(supp.):14-16). The receptors are screened againstputative ligands including known GPCR ligands and other naturallyoccurring bioactive molecules. Biological extracts from tissues,biological fluids and cell supernatants are also screened.

[0367] Various modifications and variations of the described methods andsystems of the invention will be apparent to those skilled in the artwithout departing from the scope and spirit of the invention. Althoughthe invention has been described in connection with certain embodiments,it should be understood that the invention as claimed should not beunduly limited to such specific embodiments. Indeed, variousmodifications of the described modes for carrying out the inventionwhich are obvious to those skilled in molecular biology or relatedfields are intended to be within the scope of the following claims.TABLE 1 Poly- Incyte Incyte Polypeptide Incyte nucleotide PolynucleotideProject ID SEQ ID NO: Polypeptide ID SEQ ID NO: ID 7485090 1 7485090CD149 7485090CB1 7474890 2 7474890CD1 50 7474890CB1 7474936 3 7474936CD1 517474936CB1 90012430 4 90012430CD1 52 90012430CB1 90012586 5 90012586CD153 90012586CB1 90012670 6 90012670CD1 54 90012670CB1 2880041 72880041CD1 55 2880041CB1 90012123 8 90012123CD1 56 90012123CB1 900121639 90012163CD1 57 90012163CB1 7472462 10 7472462CD1 58 7472462CB1 747487311 7474873CD1 59 7474873CB1 7475172 12 7475172CD1 60 7475172CB1 747525913 7475259CD1 61 7475259CB1 7475267 14 7475267CD1 62 7475267CB1 747527115 7475271CD1 63 7475271CB1 7475305 16 7475305CD1 64 7475305CB1 747616017 7476160CD1 65 7476160CB1 7476781 18 7476781CD1 66 7476781CB1 748760319 7487603CD1 67 7487603CB1 58015601 20 58015601CD1 68 58015601CB16541249 21 6541249CD1 69 6541249CB1 7472078 22 7472078CD1 70 7472078CB17472087 23 7472087CD1 71 7472087CB1 7472089 24 7472089CD1 72 7472089CB17474902 25 7474902CD1 73 7474902CB1 7475057 26 7475057CD1 74 7475057CB17475261 27 7475261CD1 75 7475261CB1 7475262 28 7475262CD1 76 7475262CB17475266 29 7475266CD1 77 7475266CB1 7475284 30 7475284CD1 78 7475284CB17475309 31 7475309CD1 79 7475309CB1 7477359 32 7477359CD1 80 7477359CB158004547 33 58004547CD1 81 58004547CB1 7476156 34 7476156CD1 827476156CB1 7475114 35 7475114CD1 83 7475114CB1 55003505 36 55003505CD184 55003505CB1 7474916 37 7474916CD1 85 7474916CB1 7472365 38 7472365CD186 7472365CB1 7475230 39 7475230CD1 87 7475230CB1 7475229 40 7475229CD188 7475229CB1 7477367 41 7477367CD1 89 7477367CB1 7477936 42 7477936CD190 7477936CB1 7475214 43 7475214CD1 91 7475214CB1 55036157 4455036157CD1 92 55036157CB1 7475226 45 7475226CD1 93 7475226CB1 747735346 7477353CD1 94 7477353CB1 55036208 47 55036208CD1 95 55036208CB155019501 48 55019501CD1 96 55019501CB1

[0368] TABLE 2 Polypep- tide SEQ Incyte Probability ID NO: PolypeptideID GenBank ID NO: Score Annotation 1 7485090CD1 g1256414 7.50E−41Ovarian follicle-stimulating hormone receptor [Gallus gallus] (You, S.et al. (1996) Biol. Reprod. 55: 1055-1062) 1 7485090CD1 g104417301.40E−152 leucine-rich repeat-containing G protein-coupled receptor 7[Homo sapiens] 2 7474890CD1 g5525078 6.70E−67 [Rattus norvegicus] seventransmembrane receptor Abe, J., et al. (1999) Ig-hepta, a novel memberof the G protein-coupled hepta- helical receptor (GPCR) family that hasimmunoglobulin-like repeats in a long N- terminal extracellular domainand defines a new subfamily of GPCRs. J. Biol. Chem. 274, 19957-19964 37474936CD1 g2613125 9.70E−41 [Homo sapiens] small cell vasopressinsubtype lb receptor Sugimoto, T., et al. (1994) Molecular cloning andfunctional expression of a cDNA encoding the human Vlb vasopressinreceptor. J. Biol. Chem. 269: 27088-27092 4 90012430CD1 g53597184.50E−21 [Homo sapiens] cysteinyl leukotriene receptor 5 90012586CD1g5353887 4.50E−21 Homo sapiens] cysLT1 LTD4 receptor (Lynch, K. R. etal. (1999) Nature 399: 789-793) 6 90012670CD1 g8118595 1.00E−19 [Musmusculus] leukotriene D4 receptor 7 2880041CD1 g4034486 4.30E−21 [Homosapiens] latrophilin-2 (White, G. R. et al. (1998) Oncogene 17:3513-3519) 8 90012123CD1 g8118040 2.90E−186 [Homo sapiens] orphanG-protein coupled receptor 9 90012163CD1 g8118040 6.20E−161 [Homosapiens] orphan G-protein coupled receptor 10 7472462CD1 g46802686.20E−111 [Mus musculus] odorant receptor S46 Malnic, B., et al. (1999)Cell 96: 713-723 11 7474873CD1 g15986321 1.00E−179 human breast canceramplified G-protein coupled receptor 4 (BCA-GPCR-4) [Homo sapiens] 127475172CD1 g9963968 3.70E−136 [Mus musculus] odorant receptor M72 Zheng,C., et al. (2000) Neuron 26: 81-91 13 7475259CD1 g7638409 3.40E−62 [Musmusculus] olfactory receptor P2 Zheng, C., et al. (2000) Neuron 26:81-91 14 7475267CD1 g6178010 7.30E−108 [Mus musculus] odorant receptorA16 Tsuboi, A. et al. (1999) J Neurosci. 19: 8409-8418 15 7475271CD1g6691937 2.70E−71 [Homo sapiens] bA150A6.2 (novel 7 transmembranereceptor (rhodopsin family) (olfactory receptor like) protein(hs6M1-21)) 16 7475305CD1 g6178006 2.50E−84 [Mus musculus] odorantreceptor MOR83 Tsuboi, A. et al. (1999) J Neurosci. 19: 8409-8418 177476160CD1 g1336041 5.20E−91 [Homo sapiens] HsOLF1 18 7476781CD1g4159884 1.70E−99 [Homo sapiens] similar to mouse olfactory receptor 13;similar to P34984 (PID: g464305) 19 7487603CD1 g8919695 1.80E−90 [Musmusculus] olfactory receptor Hoppe, R. et al. (2000) Genomics 66:284-295 20 58015601CD1 g2921710 3.00E−86 [Homo sapiens] olfactoryreceptor Rouguier, S. et al. (1998) Nature Genet. 18: 243-250 216541249CD1 g11908211 1.40E−88 [Homo sapiens] HOR 5′Beta14 Bulger, M. etal. (2000) Proc. Natl. Acad. Sci. U.S.A. 97: 14560-14565 22 7472078CD1g12007416 1.40E−65 [Mus musculus] m51 olfactory receptor 23 7472087CD1g11908213 1.70E−83 [Homo sapiens] HOR5′Beta12 Bulger, M. et al. (2000)Proc. Natl. Acad. Sci. U.S.A. 97: 14560-14565 24 7472089CD1 g119082137.00E−87 [Homo sapiens] HOR5′Beta12 Bulger, M. et al. (2000) Proc. Natl.Acad. Sci. U.S.A. 97: 14560-14565 25 7474902CD1 g11875778 2.40E−93 [Homosapiens] prostate specific G-protein coupled receptor; PSGR Xu, L. L. etal. (2000) Cancer Res. 60: 6568-6572 26 7475057CD1 g11908211 2.50E−75[Homo sapiens] HOR 5′Beta14 Bulger, M. et al. (2000) Proc. Natl. Acad.Sci. U.S.A. 97: 14560-14565 27 7475261CD1 g12007416 5.80E−115 [Musmusculus] m51 olfactory receptor 28 7475262CD1 g15293855 1.00E−124olfactory receptor [Homo sapiens] 29 7475266CD1 g11692555 3.00E−134 [Musmusculus] odorant receptor K40 Xie, S. Y. et at. (2000) Mamm. Genome 11:1070-1078 30 7475284CD1 g11692587 5.20E−130 [Mus musculus] odorantreceptor M37 Xie, S. Y. et at. (2000) Mamm. Genome 11: 1070-1078 317475309CD1 g11908220 1.20E−84 [Mus musculus] MOR 3′Beta4 Bulger, M. etal. (2000) Proc. Natl. Acad. Sci. U.S.A. 97: 14560-14565 32 7477359CD1g15986321 1.00E−110 human breast cancer amplified G-protein coupledreceptor 4 (BCA-GPCR-4) [Homo sapiens] 33 58004547CD1 g120074161.90E−116 [Mus musculus] m51 olfactory receptor 34 7476156CD1 g13146631.60E−94 [Canis familiaris] CfOLF2 Issel-Tarver, L. and Rine, J. (1996)Organization and expression of canine olfactory receptor genes. Proc.Natl. Acad. Sci. U.S.A. 93: 10897-10902. 35 7475114CD1 g152937631.00E−123 olfactory receptor [Homo sapiens] 36 55003505CD1 g12563932.00E−98 [Rattus norvegicus] taste bud receptor protein TB 641 Thomas,M. B. et al. (1996) Chemoreceptors expressed in taste, olfactory andmale reproductive tissues. Gene 178: 1-5. 37 7474916CD1 g28086586.50E−100 [Homo sapiens] olfactory receptor Bernot, A. et al. (1998) Atranscriptional Map of the FMF region. Genomics 50: 147-160. 387472365CD1 g4680268 6.10E−104 [Mus musculus] odorant receptor S46Malnic, B. et al. (1999) Combinatorial receptor codes for odors. Cell96: 713-723. 39 7475230CD1 g4680268 4.30E−103 [Mus musculus] odorantreceptor S46 Malnic, B. et al. (1999) Combinatorial receptor codes forodors. Cell 96: 713-723 40 7475229CD1 g15293593 1.00E−124 olfactoryreceptor [Homo sapiens] 41 7477367CD1 g15293725 1.00E−121 olfactoryreceptor [Homo sapiens] 42 7477936CD1 g6178006 7.20E−85 [Mus musculus]odorant receptor MOR83 Tsuboi A, et al. (1999) Olfactory neuronsexpressing closely linked and homologous odorant receptor genes tend toproject their axons to neighboring glomeruli on the olfactory bulb. J.Neurosci. 19: 8409-8418. 43 7475214CD1 g6178008 5.80E−99 [Mus musculus]odorant receptor MOR18 Tsuboi A, et al. (1999) Olfactory neuronsexpressing closely linked and homologous odorant receptor genes tend toproject their axons to neighboring glomeruli on the olfactory bulb. J.Neurosci. 19: 8409-8418. 44 55036157CD1 g11692519 5.60E−126 [Musmusculus] odorant receptor K11 Xie S. Y. et al. (2000) Characterizationof a cluster comprising approximately 100 odorant receptor genes inmouse. Mamm. Genome 11: 1070-1078. 45 7475226CD1 g6532001 1.00E−95odorant receptor S19 [Mus musculus] 46 7477353CD1 g12007423 1.60E−73[Mus musculus] T2 olfactory receptor 47 55036208CD1 g15293817 1.00E−120olfactory receptor [Homo sapiens] 48 55019501CD1 g15986315 1.00E−160human breast cancer amplified G-protein coupled receptor 1 (BCA-GPCR-1)[Homo sapiens]

[0369] TABLE 3 SEQ Potential ID Incyte Amino Acid PotentialGlycosylation Signature Sequences, Analytical Methods NO: Polypeptide IDResidues Phosphorylation Sites Sites Domains and Motifs and Databases 17485090CD1 726 S17 S23 S137 S145 N48 N132 7 transmembrane receptor(rhodopsin family): HMMER-PFAM S171 S219 S321 S379 N268 N305 S464-Y663S380 S425 S693 S706 N348 N419 T4 T114 T193 T278 T286 T510 T716 Y10Leucine rich repeat: HMMER-PFAM S276-K299, N180-H203, Q204-N227,K156-C179, L300-K323, Q252-D275, N132-T155, S228-P251, Q324-K347Low-density lipoprotein receptor domain: HMMER-PFAM P37-D76TRANSMEMBRANE DOMAINS: TMAP P214-L239, N387-R412, S425-R451, K456-L476,V482-N502, R508-P528, G557-M584, A609-R636, V637-P660 N-terminus isnon-cytosolic G-protein coupled receptor BL00237: BLIMPS-BLOCKSL460-P499, N570-Y581, G603-V629, N655-K671 LDL-receptor class A BL01209:BLIMPS-BLOCKS C59-E71 G-protein coupled receptors signature: PROFILESCANG471-I517 Rhodopsin-like GPCR superfamily signature BLIMPS-PRINTSPR00237: I389-S413, H422-V443, A474-I496, Q509-W530, S562-F585,V608-L632, S645-K671 G-protein coupled receptors: BLAST-DOMODM00013|P46023|759-1054: E382-Q676 DM00013|P22888|352-638: E382-K671DM00013|P35376|355-641: E382-D672 DM00013|P35409|519-807: E382-L674Leucine zipper pattern: L469-L490 MOTIFS LDL-receptor class A (LDLRA)domain MOTIFS signature: C52-C74 2 7474890CD1 924 S96 S186 S245 S254 N71N138 Signal Peptide: M1-A25 HMMER S330 S351 S373 S394 N175 N256 S572S829 S867 T304 N315 N522 T404 T431 T637 7 transmembrane receptor(Secretin family) HMMER_PFAM domain: E641-Q883 Latrophilin/CL-1-like GPSdomain: HMMER_PFAM G585-V638 TRANSMEMBRANE DOMAINS: TMAP S4-P21G549-S572 L646-V674 R682-G702 G709-T729 Q736-V756 L763-G783 A799-R827K838-H866 N-terminus is cytosolic G-protein coupled receptors family 2proteins BLIMPS_BLOCKS BL00649: T304-K331, F730-T775, C715-L740,Y801-L830, L842-G863 Secretin-like GPCR superfamily signatureBLIMPS_PRINTS PR00249: L646-W670, A717-L740, Y801-L826, V845-G865 doHORMONE; EMR1; LEUCOCYTE; BLAST_DOMO ANTIGEN; DM05221|I37225|347-738:C589-G863 DM05221|P48960|347-738: C589-G863 DM05221|A57172|465-886:P587-G863 EGF-like domain signature 2: MOTIFS C62-C75 3 7474936CD1 371S47 S81 S191 S366 N4 N250 7 transmembrane receptor (rhodopsin family):HMMER_PFAM T31 T74 T115 T352 G66-Y330 T357 TRANSMEMBRANE DOMAINS: TMAPK49-V69 M83-L103 V123-Y147 A163-R188 P209-I237 R262-Y290 A320-I337N-terminus is non-cytosolic G-protein coupled receptor signatureBL00237: BLIMPS_BLOCKS Y219-Y230, K267-F293, N322-5338, F114-P153G-protein coupled receptors signature: PROFILESCAN Y126-W171Rhodopsin-like GPCR superfamily signature BLIMPS_PRINTS PR00237:E51-W75, M83-T104, Q128-I150, Q162-I183, M211-I234, A272-L296, S312-S338Vasopressin receptor signature PR00896: BLIMPS_PRINTS K79-L90,T104-D118, M229-S241, I265-I279, RECEPTOR COUPLED GPROTEIN BLAST_PRODOMTRANSMEMBRANE GLYCOPROTEIN PHOSPHORYLATION LIPOPROTEIN PALMITATE PROTEINFAMILY PD000009: R76-G18 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|S39307|18-328: Q52-F339 G-protein coupled receptors signature:MOTIFS A134-I150 4 90012430CD1 313 S18 S225 S284 T14 N13 N17TRANSMEMBRANE DOMAINS: L36-R56, TMAP Y183 V68-T88, S100-T120, F134-R162,I188-V216, L233-Y256, A271-F299 N terminus is non-cytosolic. G-proteincoupled receptor BLIMPS_BLOCKS BL00237: W89-C128, F196-F207, H226-F252COUPLED; INTRON; T-CELLS BLAST_DOMO DM08033|P43657|1-343: L31-F293G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|P34993|36-327: L28-F293DM00013|P30872|52-338: L28-F293 DM00013|JC4618|24-304: I34-F293 590012586CD1 305 S10 S217 S276 T6 N5 N9 TRANSMEMBRANE DOMAINS: L28-R48,TMAP Y175 V60-T80, S92-T112, F126-R154, I180-V208, L225-Y248, A263-F291N terminus is non-cytosolic G-protein coupled receptor BLIMPS_BLOCKSBL00237: W81-C120, F188-F199, H218-F244 COUPLED; INTRON; T-CELLSBLAST_DOMO DM08033|P43657|1-343: L23-F285 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|P34993|36-327: L20-F285 DM00013|P30872|52-338:L20-F285 DM00013|JC4618|24-304: I26-F285 6 90012670CD1 367 S52 S72 S279S338 N67 N71 TRANSMEMBRANE DOMAINS: L90-R110, TMAP T56 T68 Y237V122-T142, S154-T174, F188-R216, I242-V270, L287-Y310, A325-F353 Nterminus is non-cytosolic G-protein coupled receptor BLIMPS_BLOCKSBL00237: W143-C182, F250-F261, H280-F306 COUPLED; INTRON; T-CELLSBLAST_DOMO DM08033|P43657|1-343: L85-F347 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|P34993|36-327: L82-F347 DM00013|P30872|52-338:L82-F347 DM00013|JC4618|24-304: I88-F347 7 2880041CD1 1124 S52 S70 S258S369 N9 N104 N135 Latrophilin/CL-1-like GPS domain: HMMER_PFAM S391 S422S594 S787 N236 N256 A500-S552 S895 S908 S944 S971 N395 N455 S1023 S1052S1064 N490 N531 T11 T131 T243 T277 N624 N883 T326 T408 T467 T475 N894N903 T492 T550 T649 T658 N911 N977 T885 T902 T999 T1063 Y437 Y753Immunoglobulin domain: G60-V129 HMMER_PFAM TRANSMEMBRANE DOMAINS:S560-H588, TMAP R592-I619, A625-A650, M677-Y703, L720-I743, Q798-L818,P825-F845 N terminus is non-cytosolic HORMONE; EMR1; LEUCOCYTE;BLAST_DOMO ANTIGEN DM05221|A57172|465-886: V503-M736DM05221|I37225|347-738: L574-E757 DM05221|P48960|347-738: L574-E757 890012123CD1 345 S8 S268 Signal Peptide: P90-A111, M48-A79 HMMER 7transmembrane receptor (metabotropic HMMER_PFAM glutamate family):W22-Q271 TRANSMEMBRANE DOMAINS: P21-R49 TMAP V59-Q87 V91-R119 W126-E146G155-V175 K200-G227 P240-C263 N-terminus is non-cytosolic PROTEIN BRIDEOF SEVENLESS BLAST_PRODOM PRECURSOR TRANSMEMBRANE GLYCOPROTEIN VISIONSIGNAL PD151485: V91-P260 9 90012163CD1 300 S8 S268 Signal Peptide:P90-A111, M48-A79 HMMER 7 transmembrane receptor (metabotropicHMMER_PFAM glutamate family): W22-Q271 TRANSMENBRANE DOMAINS: P21-R49TMAP V59-Q87 V91-R119 W126-E146 G155-V175 K200-G227 P240-I264 N-terminusis non-cytosolic PROTEIN BRIDE OF SEVENLESS BLAST_PRODOM PRECURSORTRANSMEMBRANE GLYCOPROTEIN VISION SIGNAL PD151485: V91-P260 107472462CD1 312 S3 S69 T110 T139 N5 N44 N140 Signal peptide: M1-T24SPSCAN T179 T262 7 transmembrane receptor (rhodopsin family): HMMER_PFAMG43-Y293 TRANSMEMBRANE DOMAINS: G18-T46 TMAP M67-F87 L101-A121 I143-C171I196-R224 F239-S259 P270-P290 N-terminus non-cytosolic G-protein coupledreceptors proteins BL00237: BLIMPS_BLOCKS D233-S259, P285-R301, Q92-P131G-protein coupled receptors signature PROFILESCANg_protein_receptor.prf: F104-N154 Olfactory receptor signature PR00245:BLIMPS_PRINTS M61-K82, T179-P193, F239-T254, L277-L288 RECEPTOROLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L168-V246 PUTATIVEGPROTEIN COUPLED BLAST_PRODOM RECEPTOR RAIC PD170483: V248-F308G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 P23273|18-306: H26-I307P23266|17-306: F33-I307 G45774|18-309: P20-E302 P23275|17-306: D23-R301G-protein coupled receptors signature MOTIFS M112-I128 11 7474873CD1 317S52 T196 T235 T294 N8 N45 Signal peptide: M1-G44 SPSCAN 7 transmembranereceptor (rhodopsin family): HMMER_PFAM G44-Y293 TRANSMEMBRANE DOMAINS:I34-M62 TMAP C130-L153 C172-G194 T196-I224 R237-P265 G-protein coupledreceptors proteins BL00237: BLIMPS_BLOCKS K93-P132, T235-M261, T285-K301Olfactory receptor signature PR00245: BLIMPS_PRINTS T294-L308, M62-Q83,F180-G194, F241-G256, V277-L288 OLFACTORY RECEPTOR PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD149621: T249-K310 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD000921: L169-L248 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013 P23275|17-306: S21-L308 A57069|15-304: F20-L308 P34982|17-305:S21-L308 P23266|17-306: S21-A309 12 7475172CD1 309 S67 S87 S156 S190 N5N65 Signal Peptide: M136-G155 HMMER S228 S290 T8 T18 T78 T303 7transmembrane receptor (rhodopsin family): HMMER_PFAM G41-Y289TRANSMEMBRANE DOMAINS: L23-L51 TMAP Q100-Y123 L131-E159 T197-L225N-terminus cytosolic G-protein coupled receptors proteins BL00237:BLIMPS_BLOCKS I281-K297, N90-P129 G-protein coupled receptors signaturePROFILESCAN g_protein_receptor.prf: Y102-I151 Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS PR00237: P26-C50, M59-K80,F104-I126, T140-G161, V198-L221, A236-K260, N271-K297 Olfactory receptorsignature PR00245: BLIMPS_PRINTS M59-K80, Y176-S190, F237-G252,A273-L284, S290-L304 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN PD000921:L166-L244 PD149621: V247-F309 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013 S51356|18-307: L17-V300 S29709|11-299: T18-L304 P37067|17-306:L17-K302 P23265|17-306: D22-L304 G-protein coupled receptors signatureMOTIFS A110-I126 13 7475259CD1 343 S95 S318 N33 7 transmembrane receptor(rhodopsin family): HMMER_PFAM G69-Y317 TRANSMEMBRANE DOMAINS: L61-F89TMAP Y130-D149 I163-I191 V224-I252 G260-R288 A291-Y317 N-terminuscytosolic G-protein coupled receptors proteins BL00237: BLIMPS_BLOCKSK118-P157, E259-M285, A309-K325 G-protein coupled receptors signaturePROFILESCAN g_protein_receptor.prf: Y130-G180 Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS PR00237: L54-Q78, L87-K108,F132-I154, A264-R288, T299-K325, V226-I249 Olfactory receptor signaturePR00245: BLIMPS_PRINTS L87-K108, I205-D219, F265-G280, S318-F332RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L194-L272G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 P23270|18-311: L53-H333P30954|29-316: H49-R330 P23267|20-309: P46-R330 P23274|18-306: P46-L331G-protein coupled receptors signature MOTIFS T138-I154 14 7475267CD1 311S68 S225 T79 T193 N9 Signal peptide: M1-S57 SPSCAN T289 T308 Y88 7transmembrane receptor (rhodopsin family): A42-Y288 HMMER_PFAMTRANSMEMBRANE DOMAINS: TMAP L24-C52 P59-T84 L102-Y124 Q139-L167T193-I220 C241-H261 V268-Y288 N-terminus non-cytosolic G-protein coupledreceptors proteins BL00237: BLIMPS_BLOCKS C208-Y219, T280-K296, R91-P130G-protein coupled receptors signature PROFILESCANg_protein_receptor.prf: F103-I148 Rhodopsin-like GPCR superfamilysignature BLIMPS_PRINTS PR00237: I27-S51, M60-K81, E105-I127, I141-L162,V200-L223, A237-H261, K270-K296 Olfactory receptor signature PR00245:BLIMPS_PRINTS M60-K81, F178-D192, L238-V253, V272-L283, T289-L303RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN PD000921: L167-H244 PD149621: T246-T308G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 S29710|15-301: L18-L302P23266|17-306: L18-L303 P23275|17-306: L18-L303 P37067|17-306: L18-L302G-protein coupled receptors signature MOTIFS S111-I127 15 7475271CD1 307T15 Y197 N2 N49 7 transmembrane receptor (rhodopsin family): HMMER_PFAMG38-Y287 TRANSMEMBRANE DOMAINS: TMAP L26-K46 T54-I74 I89-T114 M133-M161M195-L223 N-terminus non-cytosolic G-protein coupled receptors proteinsBL00237: BLIMPS_BLOCKS R232-R258, T279-Q295, N87-P126 G-protein coupledreceptors signature PROFILESCAN g_protein_receptor.prf: F99-A149Olfactory receptor signature PR00245: BLIMPS_PRINTS M56-K77, F174-P188,F235-S250, V271-L282, S288-F302 OLFACTORY RECEPTOR PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN PD149621:T243-V301 PD000921: L163-L242 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013 P23266|17-306: L14-A303 P23274|18-306: E19-V301 P47881|20-309:L14-I298 P37067|17-306: L14-A303 16 7475305CD1 316 S87 S93 S297 T48 N5Signal peptide: M1-S20 SPSCAN T241 T288 7 transmembrane receptor(rhodopsin family): HMMER_PFAM G41-Y287 TRANSMEMBRANE DOMAINS: TMAPQ21-I49 P58-L82 R95-Y123 N137-R165 T190-Y218 C240-C260 A267-Y287N-terminus non-cytosolic G-protein coupled receptors proteins BL00237:BLIMPS_BLOCKS K90-P129, Q24-Y35, F279-K295 G-protein coupled receptorssignature PROFILESCAN g_protein_receptor.prf: F102-L148 Rhodopsin-likeGPCR superfamily signature BLIMPS_PRINTS PR00237: L26-R50, L59-R80,L104-I126, A140-V161, M199-L222, K269-K295 Olfactory receptor signaturePR00245: BLIMPS_PRINTS F177-D191, M237-G252, V271-M282, T288-L302,L59-R80 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEINCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-I245OLFACTORY RECEPTOR PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD149621: I246-R304G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 S29710|15-301: L17-L301P23275|17-306: I23-L302 P23270|18-311: I23-L302 P37067|17-306: L17-L301G-protein coupled receptors signature MOTIFS G110-I126 17 7476160CD1 317S74 S144 S178 S195 N12 7 transmembrane receptor (rhodopsin family):HMMER_PFAM S298 T85 T170 G48-Y297 TRANSMEMBRANE DOMAINS: TMAP L39-Y67Q107-Y130 G145-R172 I204-V232 G240-R268 K279-I296 N-terminus cytosolicG-protein coupled receptors proteins BL00237: BLIMPS_BLOCKS K97-P136,E239-M265, I289-K305 Olfactory receptor signature PR00245: BLIMPS_PRINTSM66-K87, F184-D198 F245-G260, V281-L292, S298-L312 OLFACTORY RECEPTORPROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANEGLYCOPROTEIN PD000921: L173-M253 PD149621: V255-L312 PD002495: N12-D59G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 S51356|18-307: L24-L308P37067|17-306: L24-I311 S29709|11-299: S25-L312 P23266|17-306: L24-L312G-protein coupled receptors signature MOTIFS T117-I133 18 7476781CD1 317S136 S290 S309 N4 7 transmembrane receptor (rhodopsin family):HMMER_PFAM G40-Y289 TRANSMEMBRANE DOMAINS: TMAP F16-I44 H55-S71 I94-F122M135-L163 L193-L221 S238-A260 N-terminus non-cytosolic G-protein coupledreceptors proteins BL00237: BLIMPS_BLOCKS R89-P128, L206-Y217,R234-A260, N281-K297 G-protein coupled receptors signature PROFILESCANg_protein_receptor.prf: F101-A146 Olfactory receptor signature PR00245:BLIMPS_PRINTS M58-K79, F176-D190 F237-G252, L273-L284, S290-L304RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN PD000921: L165-L244 PD149621: V246-Q307G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 P23275|17-306: M22-L304P23266|17-306: E21-L304 A57069|15-304: Y34-L304 S29707|18-306: E21-K301Leucine zipper pattern L18-L39 MOTIFS 19 7487603CD1 319 S8 S67 S87 S229S263 N5 N65 7 transmembrane receptor (rhodopsin family): HMMER_PFAM S291T49 G41-Y290 TRANSMEMBRANE DOMAINS: TMAP T7-I27 L33-S53 H56-W72V142-S167 F177-L197 L207-R227 A237-S257 N-terminus non-cytosolicG-protein coupled receptors proteins BL00237: BLIMPS_BLOCKS N90-P129,L207-Y218, S235-K261, T282-K298 G-protein coupled receptors signaturePROFILESCAN g_protein_receptor.prf: Y102-G147 Olfactory receptorsignature PR00245: BLIMPS_PRINTS M59-P80, F177-D191, F238-G253,M274-L285, S291-L305 OLFACTORY RECEPTOR PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN PD149621:V247-T312 PD000921: L166-M246 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013 P23275|17-306: Y20-L305 P30954|29-316: F18-L301 P23274|18-306:Q24-L305 A57069|15-304: F17-L305 G-protein coupled receptors signatureMOTIFS T110-I126 20 58015601CD1 318 S136 S290 S309 N4 Signal peptide:M1-A23 SPSCAN 7 transmembrane receptor (rhodopsin family): HMMER_PFAMG40-Y289 TRANSMEMBRANE DOMAINS: F16-I44 H55-S71 TMAP T90-M117 I134-L162W192-I220 E231-M259 N-terminus non-cytosolic G-protein coupled receptorsproteins BL00237: BLIMPS_BLOCKS R89-P128, L206-Y217, I234-V260,N281-K297 G-protein coupled receptors signature PROFILESCANg_protein_receptor.prf: F101-T146 Olfactory receptor signature PR00245:BLIMPS_PRINTS M58-K79, L176-D190 F237-G252, L273-L284, S290-L304RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN PD000921: L165-L244 PD149621: V246-K307G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 P23275|17-306: P20-L304S51356|18-307: P20-R302 P23269|15-304: L25-L304 S29707|18-306: L29-L300G-protein coupled receptors signature MOTIFS T109-I125 21 6541249CD1 351S52 S69 S231 T110 N5 7 transmembrane receptor (rhodopsin family):HMMER_PFAM T165 T179 T263 G43-Y295 TRANSMEMBRANE DOMAINS: TMAP G18-G46Y62-N90 F96-L119 A135-L163 V196-I223 K238-F266 N-terminus non-cytosolicG-protein coupled receptors proteins BL00237: BLIMPS_BLOCKS T242-G268,P287-Q303, K92-P131 G-protein coupled receptors signature PROFILESCANg_protein_receptor.prf: F104-N154 Olfactory receptor signature PR00245:BLIMPS_PRINTS M61-N82, T179-N193, F240-V255 Melanocortin receptor familysignature BLIMPS_PRINTS PR00534: H53-L65, I128-T139, I199-F211 RECEPTOROLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L168-M247G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 G45774|18-309: P20-E304P23274|18-306: V19-L310 P23266|17-306: L31-L310 P23273|18-306: H26-L310G-protein coupled receptors signature MOTIFS M112-I128 22 7472078CD1 315S67 S87 S228 S290 T8 N5 7 transmembrane receptor (rhodopsin family):HMMER_PFAM T137 D41-Y289 TRANSMEMBRANE DOMAINS: Q21-V49 TMAP H56-T75R139-P167 S193-I220 G232-R260 P266-I288 N-terminus cytosolic G-proteincoupled receptors proteins BL00237: BLIMPS_BLOCKS I206-Y217, E231-M257,A281-N297, K90-P129 G-protein coupled receptors signature PROFILESCANg_protein_receptor.prf: Y102-C149 Visual pigments (opsins) retinalbinding site PROFILESCAN opsin.prf: S262-G315 Olfactory receptorsignature PR00245: BLIMPS_PRINTS M59-K80, I177-D191, F237-G252,I273-F284, S290-F304 Melanocortin receptor family signatureBLIMPS_PRINTS PR00534: L51-I63, I126-T137 RECEPTOR OLFACTORY PROTEINBLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD000921: L166-M245 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013 P23270|18-311: F17-K302 P23274|18-306: F28-C305P30954|29-316: F28-I300 P30955|18-305: L26-C305 G-protein coupledreceptors signature MOTIFS S110-I126 23 7472087CD1 312 S54 S138 S229T108 N5 N42 N192 Signal peptide: M1-A23 SPSCAN T162 T184 T206 7transmembrane receptor (rhodopsin family): HMMER_PFAM G41-Y291TRANSMEMBRANE DOMAINS: TMAP I15-C43 L63-G91 V141-R164 V196-I220E232-M260 K267-I289 N-terminus non-cytosolic G-protein coupled receptorsproteins BL00237: BLIMPS_BLOCKS M90-P129, A231-L257, P283-W299 G-proteincoupled receptors signature PROFILESCAN g_protein_receptor.prf:F102-I150 Olfactory receptor signature PR00245: BLIMPS_PRINTS M59-T80,S177-D191, L237-V252 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD000921: L166-I244 PUTATIVE GPROTEIN COUPLED BLAST_PRODOMRECEPTOR RA1C PD166986: F12-S54 PD170483: I244-R312 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013 G45774|18-309: P18-N308 P23273|18-306:H24-I298 S29708|18-306: E21-L307 H45774|28-318: G16-L307 Leucine zipperpattern L166-L187 MOTIFS G-protein coupled receptors signature MOTIFSM110-I126 24 7472089CD1 330 S69 S169 S190 S232 N5 Signal peptide: M1-A24SPSCAN S295 T7 T110 T209 7 transmembrane receptor (rhodopsin family):HMMER_PFAM G43-I146, I216-Y294 TRANSMEMBRANE DOMAINS: T7-Y27 TMAPC34-E54 N97-F125 I143-C171 I199-V227 F240-L260 A270-N290 N-terminusnon-cytosolic G-protein coupled receptors proteins BL00237:BLIMPS_BLOCKS R92-P131, E234-L260, P286-Q302 Olfactory receptorsignature PR00245: BLIMPS_PRINTS M61-T82, S179-D193, F240-L255 PUTATIVEGPROTEIN COUPLED BLAST_PRODOM RECEPTOR RAIC PD170483: I247-I306 RECEPTOROLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L168-I247G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 H45774|28-318: L16-L309I45774|24-314: G18-L309 D45774|24-314: G18-L309 P23269|15-304: F33-L309G-protein coupled receptors signature MOTIFS M112-I128 25 7474902CD1 314S59 S113 S235 S298 N8 N47 7 transmembrane receptor (rhodopsin family):HMMER_PFAM T56 Y65 G46-Y297 TRANSMEMBRANE DOMAINS: E26-F52 TMAP P63-W91C102-A130 V145-R170 S201-R228 K241-F269 P274-I295 N-terminusnon-cytosolic G-protein coupled receptors proteins BL00237:BLIMPS_BLOCKS R95-P134, A237-L263, P289-R305 Olfactory receptorsignature PR00245: BLIMPS_PRINTS M64-T85, S182-D196, L243-T258,M281-M292 PUTATIVE GPROTEIN COUPLED BLAST_PRODOM RECEPTOR RAIC PD170483:I250-F312 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEINCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: Y173-I250PUTATIVE GPROTEIN COUPLED BLAST_PRODOM RECEPTOR RAIC PD166986: N8-S59G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 G45774|18-309: P23-D306S29707|18-306: E26-C313 P23272|18-306: E26-C313 P23274|18-306: I22-C313Leucine zipper pattern L66-L87 MOTIFS G-protein coupled receptorssignature MOTIFS L115-I131 26 7475057CD1 320 S212 T113 T266 T314 N8Signal peptide: M1-A28 SPSCAN 7 transmembrane receptor (rhodopsinfamily): HMMER_PFAM G46-V146, P291-Y298 TRANSMEMBRANE DOMAINS: TMAPF11-W31 L41-H61 L71-W91 V97-A122 L140-V168 T200-I226 A242-G270N-terminus cytosolic G-protein coupled receptors proteins BLIMPS_BLOCKSBL00237: R95-P134, E237-S263, P290-R306 Rhodopsin-like GPCR superfamilysignature BLIMPS_PRINTS PR00237: W31-W55, M64-G85, V109-I131, C145-L166,G204-A227, A242-T266, I280-R306 Olfactory receptor signature PR00245:BLIMPS_PRINTS M64-G85, F243-I258 PUTATIVE GPROTEIN COUPLED BLAST_PRODOMRECEPTOR RAIC PD170483: I250-F313 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|P30955|18-305: V35-L309 P30953|18-306: V35-L309 P23272|18-306:V35-L309 G45774|18-309: P23-L309 27 7475261CD1 331 S67 S93 S193 S270 N57 transmembrane receptor (rhodopsin family): HMMER_PFAM S318 T78E41-Y290 TRANSMEMBRANE DOMAINS: TMAP T7-L27 F31-S51 P138-V166 A203-P229C234-R261 K272-L288 N-terminus cytosolic G-protein coupled receptorsproteins BL00237: BLIMPS_BLOCKS K90-P129, L207-Y218, T282-K298 G-proteincoupled receptors signature PROFILESCAN g_protein_receptor.prf:Y102-F147 Visual pigments (opsins) retinal binding site PROFILESCANopsin.prf: Q263-S318 Olfactory receptor signature PR00245: BLIMPS_PRINTSM59-K80, F177-D191, F238-T253, I274-L285, C291-F305 Melanocortinreceptor family signature BLIMPS_PRINTS PR00534: S51-L63, I126-T137RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN PD000921: V166-L245 PD149621: T246-G306G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 P23270|18-311: F17-K303P23267|20-309: F17-K303 P23266|17-306: P21-K303 P23274|18-306: Q24-L301G-protein coupled receptors signature MOTIFS T110-I126 28 7475262CD1 311S67 S165 S188 S193 N5 Signal peptide: M34-T54 HMMER S291 7 transmembranereceptor (rhodopsin family): HMMER_PFAM G41-Y290 TRANSMEMBRANE DOMAINS:R25-A53 TMAP A151-H176 L198-I221 F238-M258 Q270-Y290 G-protein coupledreceptors proteins BL00237: BLIMPS_BLOCKS K90-P129, I282-K298 G-proteincoupled receptors signature PROFILESCAN g_protein_receptor.prf:F102-S150 Olfactory receptor signature PR00245: BLIMPS_PRINTS M59-Q80,F177-D191, F238-G253, V274-L285, S291-W305 RECEPTOR OLFACTORY PROTEINBLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEINPD000921: L166-L245 PD149621: T246-K308 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013 S51356|18-307: L17-L301 S29709|11-299: T18-G306P23266|17-306: L17-V304 P37067|17-306: L17-L301 Leucine zipper patternL48-L69 MOTIFS G-protein coupled receptors signature MOTIFS S110-I126 297475266CD1 308 S67 S291 T78 T91 N5 N186 7 transmembrane receptor(rhodopsin family): HMMER_PFAM G41-Y290 TRANSMEMBRANE DOMAINS: TMAPF31-M59 I92-A117 I135-M163 L198-L226 G233-K261 N-terminus cytosolicG-protein coupled receptors proteins BL00237: BLIMPS_BLOCKS N90-P129,T207-Y218, E232-M258, I282-K298 G-protein coupled receptors signaturePROFILESCAN g_protein_receptor.prf: F103-F149 Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS PR00237: P26-A50, M59-K80,F104-I126, L130-L151, L199-L222, A237-K261, K272-K298 Olfactory receptorsignature PR00245: BLIMPS_PRINTS S291-L305, M59-K80 Y177-N191,F238-G253, S274-L285 OLFACTORY RECEPTOR PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD149621: V248-L305 PD000921: L166-M246 OLFACTORY RECEPTORPD049505: BLAST_PRODOM N5-L54 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013 S51356|18-307: L17-V306 S29709|11-299: T18-L305 P37067|17-306:L17-V304 P23274|18-306: A21-L305 G-protein coupled receptors signatureMOTIFS A110-I126 30 7475284CD1 298 S50 S65 S287 N3 N63 Signal peptide:M1-L53 SPSCAN 7 transmembrane receptor (rhodopsin family): HMMER_PFAMG39-C248, V277-Y286 TRANSMEMBRANE DOMAINS: TMAP S30-H54 L64-S84F101-F121 V132-L160 R195-I223 N-terminus non-cytosolic G-protein coupledreceptors proteins BL00237: BLIMPS_BLOCKS H88-P127, E230-I256, T278-K294G-protein coupled receptors signature PROFILESCANg_protein_receptor.prf: F100-T146 Olfactory receptors signature PR00245BLIMPS_PRINTS M57-K78, Y175-D189, F236-G251, I270-L281, S287-P299RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L164-L243G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 P23275|17-306: L21-K294P30955|18-305: L28-K294 S29707|18-306: L28-K294 P30953|18-306: P16-K29431 7475309CD1 317 S95 S110 S295 S310 N6 N44 7 transmembrane receptor(rhodopsin family): HMMER_PFAM T7 T232 T263 G43-Y294 TRANSMEMBRANEDOMAINS: TMAP S25-R52 M61-F89 I94-V122 V142-R167 S198-N226 L237-R265S271-P291 G-protein coupled receptors proteins BL00237: BLIMPS_BLOCKSR92-P131, A234-V260, P286-Q302 Olfactory receptor signature PR00245:BLIMPS_PRINTS M61-T82, S179-D193, L240-I255 PUTATIVE GPROTEIN COUPLEDBLAST_PRODOM RECEPTOR RA1C PD170483: V250-L306 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013 P23274|18-306: I19-L309 P30953|18-306:L36-N307 P23269|15-304: E23-L309 P23273|18-306: L36-L309 Leucine zipperpattern L168-L189 L175-L196 MOTIFS 32 7477359CD1 309 S8 S49 S67 S306T193 N5 N42 N65 Signal peptide: M1-N42 SPSCAN T291 7 transmembranereceptor (rhodopsin family): HMMER_PFAM G41-Y290 TRANSMEMBRANE DOMAlNS:TMAP P21-S49 P58-Q86 A145-P167 N195-S215 R227-V247 N-terminus cytosolicG-protein coupled receptors proteins BL00237: BLIMPS_BLOCKS K90-P129,V207-Y218, H235-Q261, T282-K298 G-protein coupled receptors signaturePROFILESCAN g_protein_receptor.prf: Y102-I147 Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS V26-Y50, M59-Q80, S104-V126,L199-T222, A237-Q261, K272-K298 Olfactory receptor signature PR00245:BLIMPS_PRINTS M59-Q80, F177-D191, F238-G253, I274-L285, T291-L305OLFACTORY RECEPTOR PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN PD000921: L166-L245 PD149621: T246-K308G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013 P23275|17-306: S18-L305A57069|15-304: F17-L305 P23274|18-306: S18-L305 S29707|18-306: P21-L301G-protein coupled receptors signature MOTIFS T110-V126 33 58004547CD1312 S67 S93 S193 S270 N5 7 transmembrane receptor (rhodopsin family):HMMER_PFAM T78 E41-Y290 TRANSMEMBRANE DOMAINS: TMAP Q24-W50 P138-V166E196-A224 C234-R261 L273-L288 N-terminus non- cytosolic G-proteincoupled receptors proteins BL00237: BLIMPS_BLOCKS T282-K298, K90-P129,L207-Y218 G-protein coupled receptors signature PROFILESCANg_protein_receptor.prf: Y102-S151 Visual pigments (opsins) retinalbinding site PROFILESCAN opsin.prf: Q263-H312 Olfactory receptorsignature PR00245: BLIMPS_PRINTS M59-K80, F177-D191, F238-T253,I274-I285, C291-L305 Melanocortin receptor family signatureBLIMPS_PRINTS PR00534: I126-T137, S51-L63 RECEPTOR OLFACTORY PROTEINBLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEINPD149621: T246-G306 PD000921: V166-L245 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013 P23270|18-311: P18-L305 P23267|20-309: L27-L305P23274|18-306: Q24-L305 P23266|17-306: L17-L305 G-protein coupledreceptors signature MOTIFS T110-I126 34 7476156CD1 310 S67, S188, S291N5, N65 Signal Peptide: M23-G41 HMMER 7 transmembrane receptor(rhodopsin family): HMMER-PFAM G41-Y290 TRANSMEMBRANE DOMAINS: TMAPQ19-I47, P58-A83, S95-F123, F135-T163, I197-I225, D271-K295; N-terminusis cytosolic G-protein coupled receptors signature PROFILESCAN(g_protein_receptor.prf): F103-G147 Olfactory receptor signature:PR00245: BLIMPS-PRINTS M59-R80, F177-D191, F238-G253, A274-L285,S291-I305 RECEPTOR OLFACTORY PROTEIN BLAST-PRODOM RECEPTOR-LIKEG-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD000921:L166-L245, PD149621: T246-K308 G-PROTEIN COUPLED RECEPTORS: BLAST-DOMODM00013|S51356|18-307: I17-A300 Signal cleavage: M45-A110 SPSCAN 357475114CD1 314 S65, S106, S186, S266, N3, N63, N83, 7 transmembranereceptor (rhodopsin family): HMMER-PFAM S289, T228 N87 S39-V256TRANSMEMBRANE DOMAINS: TMAP L6-G26, L31-V51, P56-V81, I90-Y118,C126-G150, M192-F220, F236-Y257; N-terminus is cytosolic G-proteincoupled receptor: BL00237: BLIMPS-BLOCKS N88-P127, P280-K296 G-proteincoupled receptors signature PROFILESCAN (g_protein_receptor.prf):L100-V145 Rhodopsin-like GPCR superfamily signature: BLIMPS-PRINTSPR00237: L24-T48, M57-K78, M102-I124, G197-F220, R270-K296 Olfactoryreceptor signature: PR00245: BLIMPS-PRINTS M57-K78, F175-E189,F236-I251, L272-F283, S289-L303 RECEPTOR OLFACTORY PROTEIN BLAST-PRODOMRECEPTOR-LIKE G-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY: PD000921: M164-L243, PD149621: T244-Y307 G-PROTEIN COUPLEDRECEPTORS: BLAST-DOMO DM00013|P23266|17-306: Q19-L303 G-protein coupledreceptors signature: MOTIFS G108-I124 36 55003505CD1 311 S65, S87, T288N3, N63 7 transmembrane receptor (rhodopsin family): HMMER-PFAM G39-Y287TRANSMEMBRANE DOMAINS: TMAP G20-R48, M57-M81, A90-T115, S192-I220,A236-V256, M267-Y287; N-terminus is cytosolic G-protein coupledreceptor: BL00237: BLIMPS-BLOCKS R89-P128, D231-I257, T279-K295G-protein coupled receptors signature PROFILESCAN(g_protein_receptor.prf): Y101-T147 Olfactory receptor signature:PR00245: BLIMPS-PRINTS M57-K78, Y176-D190, F237-V252, V271-L282,T288-R302 RECEPTOR OLFACTORY PROTEIN BLAST-PRODOM RECEPTOR-LIKEG-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD000921:L165-I245 G-PROTEIN COUPLED RECEPTORS: BLAST-DOMO DM00013|P23266|17-306:L15-L301 37 7474916CD1 337 S67, S188, S291, T268, N5, N8, N65, Signalcleavage: M1-G41 SPSCAN T300 N265 7 transmembrane receptor (rhodopsinfamily): HMMER-PFAM G41-Y290 TRANSMEMBRANE DOMAINS: TMAP Q23-S51,P58-L83, A99-Y123, I135-M163, S198-M226, C241-S261, E269-I289;N-terminus is not cytosolic G-protein coupled receptor: BL00237:BLIMPS-BLOCKS Q90-P129, F207-Y218, A282-K298 G-protein coupled receptorssignature PROFILESCAN (g_protein_receptor.prf): Y102-A147 Rhodopsin-likeGPCR superfamily signature: BLIMPS-PRINTS PR00237: L26-G50, M59-K80,C104-I126, V199-V222, A237-S261, S272-K298, L140-L161 Olfactory receptorsignature: PR00245: BLIMPS-PRINTS M59-K80, F177-D191, F238-G253,A274-L285, S291-L305 RECEPTOR OLFACTORY PROTEIN BLAST-PRODOMRECEPTOR-LIKE G-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY: PD000921: L166-L245, PD149621: L247-R307 G-PROTEIN COUPLEDRECEPTORS: BLAST-DOMO DM00013|P23266|17-306: Q22-S306 G-protein coupledreceptors signature: MOTIFS M110-I126 38 7472365CD1 325 S193, T110,T139, N5, N44, N108 Signal cleavage: M1-T24 SPSCAN T179 7 transmembranereceptor (rhodopsin family): HMMER-PFAM G43-Y293 TRANSMEMBRANE DOMAINS:TMAP I19-I47, A66-I86, C99-A119, N140-L168, I196-C224, S240-T262,P270-R296; N-terminus is nor cytosolic G-protein coupled receptor:BL00237: BLIMPS-BLOCKS P285-Y301, R92-P131, E233-S259 Olfactory receptorsignature: PR00245: BLIMPS-PRINTS M61-K82, T179-S193, L239-T254,L277-L288, G294-L308 RECEPTOR OLFACTORY PROTEIN BLAST-PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY: PD000921: L168-V246 G-PROTEIN COUPLED RECEPTORS: BLAST-DOMODM00013|P23266|17-306: F33-L308 39 7475230CD1 327 S324, T110, T120, N5,N322 Signal cleavage: M1-H58 SPSCAN T139, T165, T179, T260 7transmembrane receptor (rhodopsin family): HMMER-PFAM G43-P253TRANSMEMBRANE DOMAINS: TMAP E23-I51 A78-I106 N140-L168 I194-R222L234-R262 G264-V289: N-terminus is not cytosolic G-protein coupledreceptors signature PROFILESCAN (g_protein_receptor.prf): Y104-R153Olfactory receptor signature: PR00245: BLIMPS-PRINTS M61-K82, T179-S193,L237-L252 PUTATIVE GPROTEIN COUPLED BLAST-PRODOM RECEPTOR RA1C:PD170483: V246-L303, PD166986: N5-S56 G-PROTEIN COUPLED RECEPTORS:BLAST-DOMO DM00013|P23274|18-306: V19-L306 G-protein coupled receptorssignature: MOTIFS L112-I128 40 7475229CD1 313 S56, S193, T110, T139, N57 transmembrane receptor (rhodopsin family): HMMER-PFAM T179 G43-Y293TRANSMEMBRANE DOMAINS: TMAP I19-I47, L75-F96, F105-Y125, L132-L152,V196-Y224, L239-H267, Q271-H299; N-terminus is not cytosolic G-proteincoupled receptor: BL00237: BLIMPS-BLOCKS P285-R301, K92-P131, E233-S259G-protein coupled receptors signature PROFILESCAN(g_protein_receptor.prf): F104-V151 Rhodopsin-like GPCR superfamilysignature: BLIMPS-PRINTS PR00237: W28-Q52, I106-I128, K141-V162,F200-L223, A238-T262, I275-R301, M61-K82 Olfactory receptor signature:PR00245: BLIMPS-PRINTS M61-K82, T179-S193, L239-T254, L277-L288 RECEPTOROLFACTORY PROTEIN BLAST-PRODOM RECEPTOR-LIKE G-PROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD000921: L168-I246G-PROTEIN COUPLED RECEPTORS: BLAST-DOMO DM00013|P23274|18-306: I19-I307G-protein coupled receptors signature: MOTIFS M112-I128 41 7477367CD1311 S67, S233, S288, S308, N5, N65 7 transmembrane receptor (rhodopsinfamily): HMMER-PFAM T78 G41-Y287 TRANSMEMBRANE DOMAINS: TMAP E11-F31,V36-N56, E95-F123, M136-V164, T199-C227, A236-W260; N-terminus is notcytosolic G-protein coupled receptor: BL0023: BLIMPS-BLOCKS K90-P129,S234-W260, T279-K295 G-protein coupled receptors signature PROFILESCAN(g_protein_receptor.prf:) F102-I147 Rhodopsin-like GPCR superfamilysignature: BLIMPS-PRINTS PR00237: F26-S50, M59-K80, L104-I126,A236-W260, K269-K295, L140-A161, T199-L222 Olfactory receptor signature:PR00245: BLIMPS-PRINTS M59-K80, F177-D191, L237-G252, L271-L282,S288-R302 OLFACTORY RECEPTOR PROTEIN BLAST-PRODOM RECEPTOR-LIKEG-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD149621:T245-L301 G-PROTEIN COUPLED RECEPTORS: BLAST-DOMO DM00013|P23266|17-306:Q24-L301 G-protein coupled receptors signature: MOTIFS S110-I126 427477936CD1 304 S67, S137, S224, S233, N5, N65 7 transmembrane receptor(rhodopsin family): HMMER-PFAM T78, T288 G41-Y287 TRANSMEMBRANE DOMAINS:TMAP L23-F51, P58-L86, W95-Y123, L197-V225, A236-F256, S266-I286;N-terminus is cytosolic G-protein coupled receptor: BL00237:BLIMPS-BLOCKS K90-P129, S231-I257, T279-K295 G-protein coupled receptorssignature PROFILESCAN (g_protein_receptor.prf: F102-A150 Rhodopsin-likeGPCR superfamily signature: BLIMPS-PRINTS PR00237: L26-T50, M59-K80,M104-I126, V199-I222, A236-W260, K269-K295 Olfactory receptor signature:PR00245: BLIMPS-PRINTS L271-L282, T288-L302, M59-K80, F177-D191,F237-A252 OLFACTORY RECEPTOR PROTEIN BLAST-PRODOM RECEPTOR-LIKEG-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD149621:T245-L302; PD000921: L166-I244 G-PROTEIN COUPLED RECEPTORS BLAST-DOMODM00013|P30955|18-305: L26-C303 G-protein coupled receptors signature:MOTIFS S110-I126 43 7475214CD1 311 S65, S222, S227, T262, N6 7transmembrane receptor (rhodopsin family): HMMER-PFAM T286 G39-Y285TRANSMEMBRANE DOMAINS: TMAP C25-L45, S55-T75, V93-Y121, N140-F166,I192-L220, A234-F254, S264-I284; N-terminus is not cytosolic G-proteincoupled receptor: BL00237: BLIMPS-BLOCKS K88-P127, E229-M255, T277-K293G-protein coupled receptors signature PROFILESCAN(g_protein_receptor.prf): V102-T146 Rhodopsin-like GPCR superfamilysignature: BLIMPS-PRINTS PR00237: V24-C48, M57-K78, V102-I124,T138-A159, V197-L220, A234-R258, K267-K293 Olfactory receptor signature:PR00245: BLIMPS-PRINTS M57-K78, Y175-E189, L235-G250, V269-L280,T286-W300 RECEPTOR OLFACTORY PROTEIN BLAST-PRODOM RECEPTOR-LIKEG-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD000921:L164-I242; PD149621: M244-R302 G-PROTEIN COUPLED RECEPTORS: BLAST-DOMODM00013|S29710|15-301: L15-W300 G-protein coupled receptors signature:MOTIFS T108-I124 44 55036157CD1 311 S67, S93, S137, S266, N5 7transmembrane receptor (rhodopsin family): HMMER-PFAM S291, T18, T78,T87 G41-Y290 TRANSMEMBRANE DOMAINS: TMAP Q24-S52, P58-T75, Q100-Y123,Y132-I160, L197-I225, E232-L260, K272-L288: N-terminus is not cytosolicG-protein coupled receptor: BL00237: BLIMPS-BLOCKS V282-H298, N90-P129,I207-Y218, S235-Q261 Olfactory receptor signature: PR00245:BLIMPS-PRINTS M59-K80, Y177-S191, F238-G253, S274-L285, S291-L305RECEPTOR OLFACTORY PROTEIN BLAST-PRODOM RECEPTOR-LIKE G-PROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD000921: V166-I245;PD149621: S246-R308; PD049505: M1-S52 G-PROTEIN COUPLED RECEPTORS:BLAST-DOMO DM00013|S51356|18-307: L17-K307 TNF family signature: L27-L43MOTIFS 45 7475226CD1 329 S22, S126, T279, T326 N20, N60 7 transmembranereceptor (rhodopsin family): HMMER-PFAM G59-Y310 TRANSMEMBRANE DOMAINS:TMAP S41-M69 H74-S94 L103-G131 I159-C187 V212-I239 A255-G283; N-terminusis not cytosolic G-protein coupled receptor: BL00237: BLIMPS-BLOCKSH108-P147, E250-S276, P302-R318 Rhodopsin-like GPCR superfamilysignature: BLIMPS-PRINTS PR00237: W44-W68, M77-K98, I122-I144,G217-L240, A255-T279, V292-R318 Olfactory receptor signature: PR00245:BLIMPS-PRINTS M77-K98, A195-E209, F256-V271 RECEPTOR OLFACTORY PROTEINBLAST-PRODOM RECEPTOR-LIKE G-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY: PD000921: L184-I263; PD170483: I263-F325 G-PROTEINCOUPLED RECEPTORS BLAST-DOMO DM00013|P23269|15-304: I35-V324 G-proteincoupled receptors signature: MOTIFS M128-I144 46 7477353CD1 312 S66,S136, S263, S266, N5, N41, N88 7 transmembrane receptor (rhodopsinfamily): HMMER-PFAM S290, S309, T7, Y86 G40-Y289 TRANSMEMBRANE DOMAINS:TMAP I12-L32, M36-T56, S90-S116, E195-A223 G-protein coupled receptor:BL00237: BLIMPS-BLOCKS T281-M297, K89-P128, L206-Y217, K234-C260G-protein coupled receptors signature PROFILESCAN(g_protein_receptor.prf): F101-G146 Rhodopsin-like GPCR superfamilysignature: BLIMPS-PRINTS PR00237: F25-F49, M58-K79, F103-I125,V198-L221, A236-C260, K271-M297, M139-V160 Olfactory receptor signature:PR00245: BLIMPS-PRINTS M58-K79, F176-D190, Y237-A252, L273-L284,S290-I304 RECEPTOR OLFACTORY PROTEIN BLAST-PRODOM RECEPTOR-LIKEG-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD000921:I165-L244; PD149621: T245-S309 G-PROTEIN COUPLED RECEPTORS: BLAST-DOMODM00013|S29707|18-306: P18-L300 G-protein coupled receptors signature:MOTIFS A109-I125 47 55036208CD1 347 S67, S108, S188, S193, N5, N190 7transmembrane receptor (rhodopsin family): HMMER-PFAM S291, S310, T237G41-Y290 TRANSMEMBRANE DOMAINS: TMAP F18-V46, P58-L86, M94-R122,G142-G170, E197-V225, P315-I343; N-terminus is not cytosolic G-proteincoupled receptor: BL00237: BLIMPS-BLOCKS L207-Y218, T282-T298, K90-P129G-protein coupled receptors signature PROFILESCAN(g_protein_receptor.prf): F102-F147 Rhodopsin-like GPCR superfamilysignature: BLIMPS-PRINTS PR00237: F26-Y50, M59-K80, Y104-I126,I199-I222, K272-T298 Olfactory receptor signature: PR00245:BLIMPS-PRINTS M59-K80, F177-D191, F238-G253, V274-L285, S291-L305RECEPTOR OLFACTORY PROTEIN BLAST-PRODOM RECEPTOR-LIKE G-PROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD000921: S167-M246;PD149621: V247-K307 G-PROTEIN COUPLED RECEPTORS: BLAST-DOMODM00013|P23275|17-306: P23-G306 G-protein coupled receptors signature:MOTIFS S110-I126 48 55019501CD1 318 S22, S53, S71, S92, N5, N46 7transmembrane receptor (rhodopsin family): HMMER-PFAM S192, S234, T12,T197, G45-Y294 T295, T312 TRANSMEMBRANE DOMAINS: TMAP P25-S53,A106-A129, C145-C173, N199-R227, S235-Y263; N-terminus is cytosolicG-protein coupled receptor: BL00237: BLIMPS-BLOCKS K94-P133, V211-Y222,T286-K302, H239-Q265 G-protein coupled receptors signature PROFILESCAN(g_protein_receptor.prf): I107-M151 Olfactory receptor signature:PR00245: BLIMPS-PRINTS M63-Q84, F181-D195, F242-L257, I278-L289,T295-L309 RECEPTOR OLFACTORY PROTEIN BLAST-PRODOM RECEPTOR-LIKEG-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD000921:L170-L250: PD149621: V251-R311 G-PROTEIN COUPLED RECEPTORS: BLAST-DOMODM00013|P23275|17-306: I21-L309 Cell attachment sequence: R2-D4 MOTIFSG-protein coupled receptors signature: MOTIFS T114-I130

[0370] TABLE 4 Polynucleotide SEQ ID NO:/ Incyte ID/Sequence LengthSequence Fragments 49/7485090CB1/2181 1-301, 76-840, 177-789, 177-812,177-837, 177-840, 728-1023, 729-929, 729-1053, 729-1054, 815-1054,827-1054, 835-1024, 840-2181, 871-1054, 883-1054, 932-1054, 984-1702,1291-1464, 1291-1549, 1291-1566, 1291-1704, 1295-1704, 1307-1465,1318-1487, 1319-1519, 1348-1704, 1361-1601, 1362-1704, 1367-1536,1372-1704, 1378-1666, 1392-1497, 1392-1704, 1394-1649, 1396-1640,1401-1704, 1404-1704, 1429-1704, 1433-1704, 1442-1704, 1534-1704,1558-1704 50/7474890CB1/3215 1-2765, 85-152, 151-254, 151-325, 753-875,753-889, 1891-2406, 1891-2503, 1891-2541, 1891-2643, 1891-2644,1894-2643, 1896-2505, 1897-2643, 1899-2643, 1954-2642, 1999-2393,1999-2641, 1999-2643, 1999-2644, 2030-2644, 2079-2644, 2117-2748,2117-2834, 2182-2642, 2184-2302, 2385-2640, 2391-2644, 2412-2516,2478-2641, 2478-2643, 2478-2644, 2481-2644, 2619-2838, 2619-3206,2619-3210, 2619-3215, 2781-3210, 2818-3138, 2820-3210, 2833-3210,2847-3210, 2899-3210, 2932-3210, 3082-3206, 3131-3210, 3139-3210,3142-3210 51/7474936CB1/1671 1-497, 1-500, 1-508, 1-544, 1-550, 1-553,1-554, 1-564, 1-656, 1-672, 1-678, 1-679, 1-681, 1-682, 1-683, 1-686,1-688, 3-688, 5-554, 10-554, 45-554, 72-554, 93-688, 137-554, 168-554,477-554, 620-1169, 1133-1671, 1134-1671, 1236-1635, 1274-1671, 1362-167152/90012430CB1/1336 1-84, 1-754, 1-769, 205-839, 335-1336, 475-1336,477-1336, 503-1336, 517-1336, 528-1336, 529-1336, 531-1336, 542-1336,548-1336, 549-1336, 550-1336, 552-1336, 553-1336, 559-1336, 562-1336,565-1336, 567-1334, 577-1336, 580-1336, 623-910, 623-930, 623-1058,623-1130, 625-1336, 630-1336, 664-1336, 683-1336, 698-1336, 741-1336,767-1336 53/90012586CB1/1340 1-740, 1-784, 1-806, 1-896, 1-926, 2-919,4-754, 208-660, 400-1340, 567-1340 54/90012670CB1/1460 1-727, 1-839,582-1460, 635-1460 55/2880041CB1/4052 1-99, 6-570, 30-399, 30-638,30-697, 31-602, 31-700, 44-592, 123-633, 153-552, 225-552, 225-994,308-534, 598-1122, 600-967, 646-1122, 690-1076, 727-1388, 735-1410,748-965, 748-1414, 756-1399, 789-1388, 895-1363, 900-1502, 900-1548,973-1334, 977-1597, 979-1122, 1132-1343, 1137-1426, 1137-1603,1149-1321, 1149-1544, 1149-1624, 1149-1661, 1164-1401, 1189-1653,1202-2012, 1203-1454, 1217-1740, 1217-2057, 1368-1813, 1370-1695,1382-1922, 1385-1922, 1446-1999, 1472-1863, 1550-1947, 1559-2028,1603-1807, 1608-2219, 1609-1883, 1609-2029, 1659-1920, 1660-2298,1697-2399, 1706-2290, 1758-2269, 1798-2338, 1811-2064, 1819-2068,1827-2026, 1833-2105, 1861-2401, 1999-2641, 2029-2644, 2036-2524,2066-2147, 2161-2458, 2161-2466, 2161-2471, 2161-2487, 2161-2519,2161-2539, 2161-2540, 2161-2566, 2161-2569, 2161-2581, 2161-2620,2162-2628, 2163-2630, 2164-2619, 2164-2642, 2164-2651, 2176-2689,2178-2748, 2197-2678, 2217-2496, 2229-2635, 2234-2774, 2234-2795,2240-2780, 2248-2858, 2263-2597, 2266-2915, 2288-2566, 2307-3645,2337-2638, 2343-2990, 2344-2995, 2349-3006, 2356-2656, 2365-2932,2367-2966, 2374-2822, 2396-2911, 2403-2942, 2408-3084, 2415-2948,2483-3051, 2498-3146, 2502-3094, 2504-3046, 2504-3084, 2507-3131,2513-2940, 2513-2943, 2513-2950, 2523-3186, 2538-3117, 2557-3172,2565-3077, 2566-3014, 2566-3075, 2566-3080, 2566-3090, 2566-3092,2566-3106, 2566-3110, 2566-3124, 2566-3130, 2566-3146, 2566-3232,2569-2891, 2584-3183, 2588-3046, 2589-2961, 2590-2961, 2596-3188,2601-3200, 2617-3147, 2617-3212, 2630-3214, 2636-3082, 2636-3322,2640-3247, 2647-3142, 2665-2984, 2665-3139, 2667-3116, 2668-3084,2673-3264, 2678-3248, 2680-3297, 2686-3278, 2686-3328, 2698-3227,2716-3166, 2724-3288, 2757-3530, 2765-3262, 2774-3336, 2800-3220,2800-3391, 2800-3428, 2809-3192, 2811-3446, 2811-3448, 2822-3379,2825-3558, 2827-3333, 2837-3511, 2842-3515, 2844-3334, 2849-3466,2852-3418, 2856-3471, 2856-3490, 2860-3376, 2871-3376, 2873-3434,2875-3403, 2877-3407, 2881-3336, 2881-3400, 2881-3442, 2881-3447,2881-3685, 2884-3336, 2884-3501, 2885-3336, 2894-3465, 2912-3507,2923-3504, 2923-3536, 2927-3523, 2938-3281, 2939-3418, 2966-3477,2966-3524, 2969-3618, 2971-3496, 2982-3558, 2994-3552, 2996-3496,3017-3497, 3017-3513, 3028-3552, 3030-3624, 3042-3513, 3046-3612,3047-3567, 3051-3439, 3054-3596, 3070-3742, 3071-3597, 3083-3620,3083-3691, 3090-3414, 3093-3661, 3099-3664, 3100-3588, 3100-3611,3103-3644, 3107-3668, 3110-3681, 3111-3663, 3112-3561, 3114-3635,3120-3765, 3121-3744, 3130-3434, 3131-3762, 3143-3757, 3144-3722,3145-3649, 3146-3753, 3148-3758, 3165-3674, 3172-3660, 3176-3764,3178-3647, 3180-3809, 3180-3862, 3198-3683, 3201-3618, 3203-3618,3206-3630, 3212-3825, 3218-3901, 3223-3769, 3241-3952, 3244-3595,3249-3770, 3255-3794, 3258-3871, 3261-3852, 3266-3820, 3273-3906,3276-3642, 3278-3772, 3286-3862, 3306-3788, 3344-3819, 3344-405256/90012123CB1/1142 1-233, 85-853, 85-861, 85-904, 85-984, 101-760,101-762, 101-766, 101-768, 101-795, 101-816, 101-847, 101-851, 101-857,101-862, 102-858, 104-862, 104-873, 104-877, 105-748, 264-1142,351-1124, 352-1142, 358-1142, 366-1141, 395-1142, 415-1141, 433-1141,464-1124, 527-1142 57/90012163CB1/1054 1-233, 85-853, 85-861, 85-892,85-904, 101-760, 101-762, 101-766, 101-768, 101-795, 101-816, 101-847,101-851, 101-857, 101-862, 101-889, 104-862, 104-878, 104-882, 105-748,238-1054, 299-1054, 302-1054, 308-1054, 345-1054, 428-105458/7472462CB1/1251 1-1251, 458-665, 458-876 59/7474873CB1/1187 1-1187,310-731 60/7475172CB1/1201 1-1201, 231-418 61/7475259CB1/2436 1-2436,1001-2436, 1170-1294 62/7475267CB1/1050 1-563, 1-1050, 648-93863/7475271CB1/1451 1-201, 51-1451, 237-1043 64/7475305CB1/1288 1-128865/7476160CB1/1271 1-1271, 178-1136, 489-632 66/7476781CB1/954 1-947,71-602, 71-617, 71-663, 71-781, 71-782, 71-795, 75-832, 92-634, 92-719,104-832, 111-832, 117-820, 129-644, 129-764, 129-832, 135-249, 135-832,136-781, 136-832, 158-243, 340-743, 340-764, 340-771, 340-788, 340-795,340-832, 340-884, 341-708, 341-788, 341-832, 341-841, 341-844, 341-878,341-887, 341-907, 347-795, 348-878, 367-661, 367-709, 452-602, 452-636,452-652, 452-665, 452-672, 452-708, 452-743, 452-782, 452-795, 452-832,456-708, 456-832, 456-887, 479-618, 479-954, 493-795, 520-602, 526-602,526-832, 557-907, 559-907, 577-907, 582-678, 589-907 67/7487603CB1/14511-1069, 301-1451, 428-1069 68/58015601CB1/1511 1-1511, 194-80969/6541249CB1/1056 1-1056, 620-926, 632-926 70/7472078CB1/1351 1-1351,798-1166 71/7472087CB1/1201 1-1201, 355-1053 72/7472089CB1/1251 1-1251,185-753 73/7474902CB1/1221 1-1221, 656-1014 74/7475057CB1/1276 1-1276,320-977, 337-618, 338-977 75/7475261CB1/1509 1-1509, 201-1509, 401-1309,422-1309 76/7475262CB1/1301 1-1301, 151-1301, 251-1301, 405-122177/7475266CB1/1051 1-1051, 130-968 78/7475284CB1/1490 1-251, 1-293,1-318, 1-342, 1-375, 1-381, 1-386, 1-420, 1-428, 1-434, 1-435, 1-504,1-524, 1-527, 1-678, 1-730, 4-546, 7-519, 7-730, 11-730, 37-730, 40-730,50-528, 107-528, 110-528, 113-528, 118-528, 156-528, 181-528, 212-528,306-528, 340-1490, 392-1273, 693-889 79/7475309CB1/1288 1-1288, 415-814,416-814, 417-520, 417-805, 417-807, 417-814, 419-814, 667-81480/7477359CB1/1124 1-1124, 101-1030 81/58004547CB1/1447 1-1436, 16-1436,169-946, 180-946, 186-946, 189-946, 193-946, 196-946, 223-946, 251-946,258-946, 274-946, 337-946, 496-964, 633-1305, 635-755, 635-946,635-1028, 635-1033, 635-1035, 635-1058, 635-1069, 635-1135, 635-1156,635-1161, 635-1171, 635-1297, 635-1299, 635-1361, 635-1377, 635-1424,635-1447, 637-946, 637-1367, 638-1362, 726-1439, 733-1361, 754-1360,798-1447, 836-1422, 843-1360, 1069-1447, 1117-1410, 1135-1447,1153-1447, 1170-1291 82/7476156CB1/1026 1-144, 94-138, 94-146, 94-298,94-486, 94-588, 94-701, 94-702, 94-1026, 96-565, 106-702, 119-701,124-680, 129-702, 131-702, 150-702, 151-702, 157-696, 163-702, 191-702,203-702, 223-702, 368-702, 665-818 83/7475114CB1/1481 1-1481, 446-104584/55003505CB1/1106 1-1106, 2-287, 98-322, 105-322, 110-32285/7474916CB1/1601 1-1601, 18-1601 86/7472365CB1/1327 1-1327, 101-1327,421-1166 87/7475230CB1/1163 1-1163, 344-1048 88/7475229CB1/1121 1-1121,299-1042 89/7477367CB1/958 1-901, 263-958 90/7477936CB1/1101 1-1101,271-508, 596-677 91/7475214CB1/1192 1-1192, 366-910 92/55036157CB1/13411-1341, 201-1341, 362-686, 969-1190 93/7475226CB1/1114 1-1107, 682-111494/7477353CB1/960 1-960, 13-927, 259-435, 500-557, 589-92895/55036208CB1/1269 1-1269, 201-1269, 377-576, 377-579, 383-576,383-579, 386-579 96/55019501CB1/2197 1-2197, 201-2197, 429-493, 907-1162

[0371] TABLE 5 Polynucleotide SEQ ID NO: Incyte Project ID:Representative Library 49 7485090CB1 ADRETUT07 50 7474890CB1 PROSTMY0152 90012430CB1 MONOTXN05 55 2880041CB1 MIXDUNB01 56 90012123CB1LUNGTUT09 57 90012163CB1 LUNGTUT09 66 7476781CB1 GPCRGSV02 69 6541249CB1LNODNON02 74 7475057CB1 SINITMR01 95 55036208CB1 GPCRDPV02

[0372] TABLE 6 Library Vector Library Description ADRETUT07 pINCYLibrary was constructed using RNA isolated from adrenal tumor tissueremoved from a 43-year-old Caucasian female during a unilateraladrenalectomy. Pathology indicated pheochromocytoma. GPCRDPV02 PCR2-Library was constructed using pooled cDNA from different donors. cDNAwas generated using mRNA isolated from TOPOTA the following: aorta,cerebellum, lymph nodes, muscle, tonsil (lymphoid hyperplasia), bladdertumor (invasive grade 3 transitional cell carcinoma.), breast(proliferative fibrocystic changes without atypia characterized byepithilial ductal hyperplasia, testicle tumor (embryonal carcinoma),spleen, ovary, parathyroid, ileum, breast skin, sigmoid colon, penistumor (fungating invasive grade 4 squamous cell carcinoma), fetal lung,breast, fetal small intestine, fetal liver, fetal pancreas, fetal lung,fetal skin, fetal penis, fetal bone, fetal ribs, frontal brain tumor(grade 4 gemistocytic astrocytoma), ovary (stromal hyperthecosis),bladder, bladder tumor (invasive grade 3 transitional cell carcinoma),stomach, lymph node tumor (metastatic basaloid squamous cell carcinoma),tonsil (reactive lymphoid hyperplasia), periosteum from the tibia, fetalbrain, fetal spleen, uterus tumor, endometrial (grade 3 adenosquamouscarcinoma), seminal vesicle, liver, aorta, adrenal gland, lymph node(metastatic grade 3 squamous cell carcinoma), glossal muscle, esophagus,esophagus tumor (invasive grade 3 adenocarcinoma), ileum, pancreas, softtissue tumor from the skull (grade 3 ependymoma), transverse colon,(benign familial polyposis), rectum tumor (grade 3 colonicadenocarcinoma), rib tumor, (metastatic grade 3 osteosarcoma), lung,heart, placenta, thymus, stomach, spleen (splenomegaly with congestion),uterus, cervix (mild chronic cervicitis with focal squamous metaplasia),spleen tumor (malignant lymphoma, diffuse large cell type, B-cellphenotype with abundant reactive T-cells and marked granulomatousresponse), umbilical cord blood mononuclear cells, upper lobe lungtumor, (grade 3 squamous cell carcinoma), endometrium (secretory phase),liver, liver tumor (metastatic grade 2 neuroendocrine carcinoma), colon,umbilical cord blood, Th1 cells, nonactivated, umbilical cord blood, Th2cells, nonactivated, coronary artery endothelial cells (untreated),coronary artery smooth muscle cells, (untreated), coronary artery smoothmuscle cells (treated with TNF & IL-1 10 ng/ml each for 20 hrs), bladder(mild chronic cystitis), epiglottis, breast skin, small intestine, fetalprostate stroma fibroblasts, prostate epithelial cells (PrEC cells),fetal adrenal glands, fetal liver, kidney transformed embryonal cellline (293- EBNA) (untreated), kidney transformed embryonal cell line(293-EBNA) (treated with 5Aza-2deoxycytidine for 72 hours), mammaryepithelial cells, (HMEC cells), peripheral blood monocytes (treated withIL-10 at time 0, 10 ng/ml, LPS was added at 1 hour at 5 ng/ml.Incubation 24 hrs), peripheral blood monocytes (treated with anti-IL-10at time 0, 10 ng/ml, LPS was added at 1 hour at 5 ng/ml. Incubation 24hrs), spinal cord, base of medulla (Huntington's chorea), thigh and armmuscle (ALS), breast skin fibroblast (untreated), breast skin fibroblast(treated with 9CIS Retinoic Acid 1 μM for 20 hrs), breast skinfibroblast (treated with TNF-alpha & IL-1 beta, 10 ng/ml each for 20hrs), fetal liver mast cells, hematopoietic (Mast cells prepared fromhuman fetal liver hematopoietic progenitor cells (CD34+ stem cells)cultured in the presence of hIL-6 and hSCF for 18 days), epitheliallayer of colon, bronchial epithelial cells (treated for 20 hrs with 20%smoke conditioned media), lymph node, pooled peripheral bloodmononuclear cells (untreated), pooled brain segments: striatum, globuspallidus and posterior putamen (Alzheimer's Disease), pituitary gland,umbilical cord blood, CD34+ derived dendritic cells (treated with SCF,GM-CSF & TNF alpha, 13 days), umbilical cord blood, CD34+ deriveddendritic cells (treated with SCF, GM-CSF & TNF alpha, 13 days followedby PMA/Ionomycin for 5 hours), small intestine, rectum, bone marrowneuroblastoma cell line (SH-SY5Y cells, treated with 6-Hydroxydopamine100 uM for 8 hours), bone marrow, neuroblastoma cell line (SH-SY5Ycells, untreated), brain segments from one donor: amygdala, entorhinalcortex, globus pallidus, substantia innominata, striatum, dorsal caudatenucleus, dorsal putamen, ventral nucleus accumbens, archaecortex(hippocampus anterior and posterior), thalamus, nucleus raphe magnus,periaqueductal gray, midbrain, substantia nigra, and dentate nucleus,pineal gland (Alzheimer's Disease), preadipocytes (untreated),preadipocytes (treated with a peroxisome proliferator-activated receptorgamma agonist, 1 microM, 4 hours), pooled prostate (Adenofibromatoushyperplasia), pooled kidney, pooled adipocytes (untreated), pooledadipocytes (treated with human insulin), pooled mesentaric and abdomenalfat, pooled adrenal glands, pooled thyroid (normal and adenomatoushyperplasia), pooled spleen (normal and with changes consistent withidiopathic thrombocytopenic purpura), pooled right and left breast,pooled lung, pooled nasal polyps, pooled fat, pooled synovium (normaland rhumatoid arthritis), pooled brain (meningioma, gemistocyticastrocytoma. and Alzheimer's disease), pooled fetal colon, pooled colon:ascending, descending (chronic ulcerative colitis), and rectal tumor(adenocarcinoma), pooled esophagus, normal and tumor (invasive grade 3adenocarcinoma), pooled breast skin fibroblast (one treated w/9CISRetinoic Acid and the other with TNF-alpha & IL-1 beta), pooledgallbladder (acute necrotizing cholecystitis with cholelithiasis(clinically hydrops), acute hemorrhagic cholecystitis withcholelithiasis, chronic cholecystitis and cholelithiasis), pooled fetalheart, (Patau's and fetal demise), pooled neurogenic tumor cell line,SK-N-MC, (neuroepitelioma, metastasis to supra-orbital area, untreated)and neuron, NT-2 cell line, (treated with mouse leptin at 1 μg/ml and9cis retinoic acid at 3.3 μM for 6 days), pooled ovary (normal andpolycystic ovarian disease), pooled prostate, (Adenofibromatoushyperplasia), pooled seminal vesicle, pooled small intestine, pooledfetal small intestine, pooled stomach and fetal stomach, prostateepithelial cells, pooled testis (normal and embryonal carcinoma), pooleduterus, pooled uterus tumor (grade 3 adenosquamous carcinoma andleiomyoma), pooled uterus, endometrium, and myometrium, (normal andadenomatous hyperplasia with squamous metaplasia and focal atypia),pooled brain: (temporal lobe meningioma, cerebellum and hippocampus(Alzheimer's Disease), and pooled skin. GPCRGSV02 PBLUEII(SK−) Librarywas constructed using RNA isolated from a pool of mixed tissues removedfrom male and female donors ranging in age from an 18 week fetus to an85 year-old. Tissues in the pool included breast, ovary (stromalhyperthecosis), stomach (chronic gastritis), lung (fetal), heart(fetal), kidney, liver, ileum, transverse colon (benign familialpolyposis), myometrium, placenta (16 weeks), thymus, umbilical cordblood mononuclear cells treated with G-CSF, colon, small intestine,adrenal glands (fetal), cerebellum (Huntington's), colon epitheliallayer, lymph node, striatum, globus pallidus and posterior putamen(Alzheimer's), rectum, fallopian tube tumor (Mixed endometrioid (80%)and serous (20%) adenocarcinoma, poorly differentiated.), amygdala,entorhinal cortex, globus pallidus, substantia innominata, striatum,dorsal putamen, ventral nucleus accumbens, frontal and anteriorcingulate allocortex and neocortex, posterior cingulate allocortex,anterior and posterior hippocampus archaecortex, auditory neocortex,frontal neocortex, visual primary neocortex, nucleus raphe magnus,periaqueductal gray, midbrain, substantia nigra, dentate nucleus,prostate (adenofibromatous hyperplasia), aorta, coronary arteries(coronary artery disease), adrenal glands, spleen (idiopathicthrombocytopenic purpura), spleen, lung, and nasal polyps. LNODNON02pINCY This normalized lymph node tissue library was constructed from .56million independent clones from a lymph node tissue library. StartingRNA was made from lymph node tissue removed from a 16-month-oldCaucasian male who died from head trauma. Serologies were negative.Patient history included bronchitis. Patient medications includedDopamine, Dobutamine, Vancomycin, Vasopressin, Proventil, and Atarax.The library was normalized in two rounds using conditions adapted fromSoares et al., PNAS (1994) 91: 9228-9932 and Bonaldo et al. (1996)Genome Research 6: 791, except that a significantly longer (48hours/round) reannealing hybridization was used. LUNGTUT09 pINCY Librarywas constructed using RNA isolated from lung tumor tissue removed from a68-year-old Caucasian male during segmental lung resection. Pathologyindicated invasive grade 3 squamous cell carcinoma and a metastatictumor. Patient history included type II diabetes, thyroid disorder,depressive disorder, hyperlipidemia, esophageal ulcer, and tobacco use.MIXDUNB01 pINCY Library was constructed using RNA isolated frommyometrium removed from a 41-year-old Caucasian female (A) duringvaginal hysterectomy with a dilatation and curettage and untreatedsmooth muscle cells removed from the renal vein of a 57 year-oldCaucasian male. Pathology for donor A indicated the myometrium andcervix were unremarkable. The endometrium was secretory and containedfragments of endometrial polyps. Benign endo- and ectocervical mucosawere identified in the endocervix. Pathology for the associated tumortissue indicated uterine leiomyoma. Medical history included anunspecified menstrual disorder, ventral hernia, normal delivery, abenign ovarian neoplasm, and tobacco abuse in donor A. Previoussurgeries included a bilateral destruction of fallopian tubes, removalof a solitary ovary, and an exploratory laparotomy in donor A.Medications included ferrous sulfate in donor A. MONOTXN05 pINCY Thisnormalized treated monocyte cell tissue library was constructed from1.03 million independent clones from a monocyte tissue library. StartingRNA was made from RNA isolated from treated monocytes from peripheralblood removed from a 42-year-old female. The cells were treated withinterleukin-10 (IL-10) and lipopolysaccharide (LPS). The library wasnormalized in two rounds using conditions adapted from Soares et al.,PNAS (1994) 91: 9228-9232 and Bonaldo et al. (1996) Genome Research 6:791, except that a significantly longer (48 hours/round) reannealinghybridization was used. PROSTMY01 pINCY This large size-fractionatedcDNA and normalized library was constructed using RNA isolated fromdiseased prostate tissue removed from a 55-year-old Caucasian maleduring closed prostatic-biopsy, radical prostatectomy, and regionallymph node excision. Pathology indicated adenofibromatous hyperplasia.Pathology for the matched tumor tissue indicated adenocarcinoma Gleasongrade 4 forming a predominant mass involving the left side peripherallywith extension into the right posterior superior region. The tumorinvaded the capsule and perforated the capsule to involve periprostatictissue in the left posterior superior region. The left inferiorposterior and left superior posterior surgical margins are positive. Oneleft pelvic lymph node is metastatically involved. Patient historyincluded calculus of the kidney. Family history included lung cancer andbreast cancer. The size-selected library was normalized in 1 round usingconditions adapted from Soares et al., PNAS (1994) 91: 9228-9232 andBonaldo et al., Genome Research (1996) 6: 791. SINITMR01 PCDNA2.1 Thisrandom primed library was constructed using RNA isolated from ileumtissue removed from a 70-year-old Caucasian female during righthemicolectomy, open liver biopsy, flexible sigmoidoscopy, colonoscopy,and permanent colostomy. Pathology for the matched tumor tissueindicated invasive grade 2 adenocarcinoma forming an ulcerated mass,situated 2 cm distal to the ileocecal valve. Patient history included amalignant breast neoplasm, type II diabetes, hyperlipidemia, viralhepatitis, an unspecified thyroid disorder, osteoarthritis, a malignantskin neoplasm, deficiency anemia, and normal delivery. Family historyincluded breast cancer, atherosclerotic coronary artery disease, benignhypertension, cerebrovascular disease, ovarian cancer, andhyperlipidemia.

[0373] TABLE 7 Program Description Reference Parameter Threshold ABI Aprogram that removes vector sequences and masks Applied Biosystems,FACTURA ambiguous bases in nucleic acid sequences. Foster City, CA. ABI/A Fast Data Finder useful in Applied Biosystems, Mismatch < 50% PARACELcomparing and annotating amino Foster City, CA; FDF acid or nucleic acidsequences. Paracel Inc., Pasadena, CA. ABI A program that assemblesnucleic acid sequences. Applied Biosystems, AutoAssembler Foster City,CA. BLAST A Basic Local Alignment Search Tool useful in Altschul, S.F.et al. (1990) ESTs: Probability sequence similarity search for aminoacid and nucleic J. Mol. Biol. 215: 403-410; value = 1.0E−8 acidsequences. BLAST includes five functions: Altschul, S.F. et al. (1997)or less; blastp, blastn, blastx, tblastn, and tblastx. Nucleic AcidsRes. 25: 3389-3402. Full Length sequences: Probability value = 1.0E−10or less FASTA A Pearson and Lipman algorithm that searches for Pearson,W. R. and ESTs: fasta E similarity between a query sequence and a groupof D. J. Lipman (1988) Proc. Natl. value = 1.06E−6; sequences of thesame type. FASTA comprises as Acad Sci. USA 85: 2444-2448; AssembledESTs: fasta least five functions: fasta, tfasta, fastx, tfastx, andPearson, W. R. (1990) Methods Enzymol. 183: 63-98; Identity = 95% orssearch. and Smith, T. F. and M. S. Waterman (1981) greater and Adv.Appl. Math. 2: 482-489. Match length = 200 bases or greater; fastx Evalue = 1.0E−8 or less; Full Length sequences: fastx score = 100 orgreater BLIMPS A BLocks IMProved Searcher that matches a Henikoff, S.and J. G. Henikoff (1991) Probability value = sequence against those inBLOCKS, PRINTS, Nucleic Acids Res. 19: 6565-6572; Henikoff, 1.0E−3 orless DOMO, PRODOM, and PFAM databases to search J. G. and S. Henikoff(1996) Methods for gene families, sequence homology, and structuralEnzymol. 266: 88-105; and Attwood, T. K. et fingerprint regions. al.(1997) J. Chem. Inf. Comput. Sci. 37: 417-424. HMMER An algorithm forsearching a query sequence against Krogh, A. et al. (1994) J. Mol. Biol.PFAM hidden Markov model (HMM)-based databases of 235: 1501-1531;Sonnhammer, E. L. L. et al. hits: protein family consensus sequences,such as PFAM. (1988) Nucleic Acids Res. 26: 320-322; Probability value =Durbin, R. et al. (1998) Our World View, in 1.0E−3 or less a Nutshell,Cambridge Univ. Press, pp. 1-350. Signal peptide hits: Score = 0 orgreater ProfileScan An algorithm that searches for structural andGribskov, M. et al. (1988) CABIOS 4: 61-66; Normalized quality sequencemotifs in protein sequences that match Gribskov, M. et al. (1989)Methods score ≧ GCG sequence patterns defined in Prosite. Enzymol. 183:146-159; Bairoch, A. et al. specified “HIGH” (1997) Nucleic Acids Res.25: 217-221. value for that particular Prosite motif. Generally, score =1.4-2.1. Phred A base-calling algorithm that examines automated Ewing,B. et al. (1998) Genome Res. 8: 175-185; sequencer traces with highsensitivity and probability. Ewing, B. and P. Green (1998) Genome Res.8: 186-194. Phrap A Phils Revised Assembly Program including Smith, T.F. and M. S. Waterman (1981) Adv. Score = 120 or greater; SWAT andCrossMatch, programs based on efficient Appl. Math. 2: 482-489; Smith,T. F. and Match length = implementation of the Smith-Waterman algorithm,M. S. Waterman (1981) J. Mol. Biol. 147: 195-197; 56 or greater usefulin searching sequence homology and and Green, P., University ofassembling DNA sequences. Washington, Seattle, WA. Consed A graphicaltool for viewing and editing Phrap Gordon, D. et al. (1998) Genome Res.8: 195-202. assemblies. SPScan A weight matrix analysis program thatscans protein Nielson, H. et al. (1997) Protein Engineering Score = 3.5or greater sequences for the presence of secretory signal  10: 1-6;Claverie, J. M. and S. Audic (1997) peptides. CABIOS 12: 431-439. TMAP Aprogram that uses weight matrices to delineate Persson, B. and P. Argos(1994) J. Mol. Biol. transmembrane segments on protein sequences and237: 182-192; Persson, B. and P. Argos determine orientation. (1996)Protein Sci. 5: 363-371. TMHMMER A program that uses a hidden Markovmodel (HMM) Sonnhammer, E.L. et al. (1998) Proc. Sixth to delineatetransmembrane segments on protein Intl. Conf. on Intelligent Systems forMol. sequences and determine orientation. Biol., Glasgow et al., eds.,The Am. Assoc. for Artificial Intelligence Press, Menlo Park, CA, pp.175-182. Motifs A program that searches amino acid sequences forBairoch, A. et al. (1997) Nucleic Acids Res. patterns that matched thosedefined in Prosite.  25: 217-221; Wisconsin Package Program Manual,version 9, page M51-59, Genetics Computer Group, Madison, WI.

[0374]

0 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 96 <210> SEQ ID NO 1<211> LENGTH: 726 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 7485090CD1 <400> SEQUENCE: 1 Met Gln Lys Thr Lys Gln Asp Glu Asp TyrGlu Arg Ala Ile Gly 1 5 10 15 Phe Ser Val Lys Met Asp Asp Ser Asp SerAsp Phe Ala Leu Thr 20 25 30 Gln Gly Ser Met Ile Thr Pro Ser Cys Gln LysGly Tyr Phe Pro 35 40 45 Cys Gly Asn Leu Thr Lys Cys Leu Pro Arg Ala PheHis Cys Asp 50 55 60 Gly Lys Asp Asp Cys Gly Asn Gly Ala Asp Glu Glu AsnCys Gly 65 70 75 Asp Thr Ser Gly Trp Ala Thr Ile Phe Gly Thr Val His GlyAsn 80 85 90 Ala Asn Ser Val Ala Leu Thr Gln Glu Cys Phe Leu Lys Gln Tyr95 100 105 Pro Gln Cys Cys Asp Cys Lys Glu Thr Glu Leu Glu Cys Val Asn110 115 120 Gly Asp Leu Lys Ser Val Pro Met Ile Ser Asn Asn Val Thr Leu125 130 135 Leu Ser Leu Lys Lys Asn Lys Ile His Ser Leu Pro Asp Lys Val140 145 150 Phe Ile Lys Tyr Thr Lys Leu Lys Lys Ile Phe Leu Gln His Asn155 160 165 Cys Ile Arg His Ile Ser Arg Lys Ala Phe Phe Gly Leu Cys Asn170 175 180 Leu Gln Ile Leu Tyr Leu Asn His Asn Cys Ile Thr Thr Leu Arg185 190 195 Pro Gly Ile Phe Lys Asp Leu His Gln Leu Thr Trp Leu Ile Leu200 205 210 Asp Asp Asn Pro Ile Thr Arg Ile Ser Gln Arg Leu Phe Thr Gly215 220 225 Leu Asn Ser Leu Phe Phe Leu Ser Met Val Asn Asn Tyr Leu Glu230 235 240 Ala Leu Pro Lys Gln Met Cys Ala Gln Met Pro Gln Leu Asn Trp245 250 255 Val Asp Leu Glu Gly Asn Arg Ile Lys Tyr Leu Thr Asn Ser Thr260 265 270 Phe Leu Ser Cys Asp Ser Leu Thr Val Leu Asp Leu Ser Ser Asn275 280 285 Thr Ile Thr Glu Leu Ser Pro His Leu Phe Lys Asp Leu Lys Leu290 295 300 Leu Gln Lys Leu Asn Leu Ser Ser Asn Pro Leu Met Tyr Leu His305 310 315 Lys Asn Gln Phe Glu Ser Leu Lys Gln Leu Gln Ser Leu Asp Leu320 325 330 Glu Arg Ile Glu Ile Pro Asn Ile Asn Thr Arg Met Phe Gln Pro335 340 345 Met Lys Asn Leu Ser His Ile Pro Cys Tyr Phe Lys Asn Phe Arg350 355 360 Tyr Cys Ser Tyr Ala Pro His Val Arg Ile Cys Met Pro Leu Thr365 370 375 Asp Gly Ile Ser Ser Phe Glu Asp Leu Leu Ala Asn Asn Ile Leu380 385 390 Arg Ile Phe Val Trp Val Ile Ala Phe Ile Thr Cys Phe Gly Asn395 400 405 Leu Phe Val Ile Gly Met Arg Ser Phe Ile Lys Ala Glu Asn Thr410 415 420 Thr His Ala Met Ser Ile Lys Ile Leu Cys Cys Ala Asp Cys Leu425 430 435 Met Gly Val Tyr Leu Phe Phe Val Gly Ile Phe Asp Ile Lys Tyr440 445 450 Arg Gly Gln Tyr Gln Lys Tyr Ala Leu Leu Trp Met Glu Ser Val455 460 465 Gln Cys Arg Leu Met Gly Phe Leu Ala Met Leu Ser Thr Glu Val470 475 480 Ser Val Leu Leu Leu Thr Tyr Leu Thr Leu Glu Lys Phe Leu Val485 490 495 Ile Val Phe Pro Phe Ser Asn Ile Arg Pro Gly Lys Arg Gln Thr500 505 510 Ser Val Ile Leu Ile Cys Ile Trp Met Ala Gly Phe Leu Ile Ala515 520 525 Val Ile Pro Phe Trp Asn Lys Asp Tyr Phe Gly Asn Phe Tyr Gly530 535 540 Lys Asn Gly Val Cys Phe Pro Leu Tyr Tyr Asp Gln Thr Glu Asp545 550 555 Ile Gly Ser Lys Gly Tyr Ser Leu Gly Ile Phe Leu Gly Val Asn560 565 570 Leu Leu Ala Phe Leu Ile Ile Val Phe Ser Tyr Ile Thr Met Phe575 580 585 Cys Ser Ile Gln Lys Thr Ala Leu Gln Thr Thr Glu Val Arg Asn590 595 600 Cys Phe Gly Arg Glu Val Ala Val Ala Asn Arg Phe Phe Phe Ile605 610 615 Val Phe Ser Asp Ala Ile Cys Trp Ile Pro Val Phe Val Val Lys620 625 630 Ile Leu Ser Leu Phe Arg Val Glu Ile Pro Asp Thr Met Thr Ser635 640 645 Trp Ile Val Ile Phe Phe Leu Pro Val Asn Ser Ala Leu Asn Pro650 655 660 Ile Leu Tyr Thr Leu Thr Thr Asn Phe Phe Lys Asp Lys Leu Lys665 670 675 Gln Leu Leu His Lys His Gln Arg Lys Ser Ile Phe Lys Ile Lys680 685 690 Lys Lys Ser Leu Ser Thr Ser Ile Val Trp Ile Glu Asp Ser Ser695 700 705 Ser Leu Lys Leu Gly Val Leu Asn Lys Ile Thr Leu Gly Asp Ser710 715 720 Ile Met Lys Pro Val Ser 725 <210> SEQ ID NO 2 <211> LENGTH:924 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7474890CD1<400> SEQUENCE: 2 Met Val Cys Ser Ala Ala Pro Leu Leu Leu Leu Ala ThrThr Leu 1 5 10 15 Pro Leu Leu Gly Ser Pro Val Ala Gln Ala Ser Gln ProGly Gln 20 25 30 Ser Gln Ala Gly Gly Glu Ser Gly Ser Gly Gln Leu Leu AspGln 35 40 45 Glu Asn Gly Ala Gly Glu Cys Asn Val Asn His Lys Gly Asn Phe50 55 60 Tyr Cys Ala Cys Leu Ser Gly Tyr Gln Trp Asn Thr Ser Ile Cys 6570 75 Leu His Tyr Pro Pro Cys Gln Ser Leu His Asn His Gln Pro Cys 80 8590 Gly Cys Leu Val Phe Ser His Pro Glu Pro Gly Tyr Cys Gln Leu 95 100105 Leu Pro Pro Val Pro Gly Ile Leu Asn Leu Asn Ser Gln Leu Gln 110 115120 Met Pro Gly Asp Thr Leu Ser Leu Thr Leu His Leu Ser Gln Glu 125 130135 Ala Thr Asn Leu Ser Trp Phe Leu Arg His Pro Gly Ser Pro Ser 140 145150 Pro Ile Leu Leu Gln Pro Gly Thr Gln Val Ser Val Thr Ser Ser 155 160165 His Gly Gln Ala Ala Leu Ser Val Ser Asn Met Ser His His Trp 170 175180 Ala Gly Glu Tyr Met Ser Cys Phe Glu Ala Gln Gly Phe Lys Trp 185 190195 Asn Leu Tyr Glu Val Val Arg Val Pro Leu Lys Ala Thr Asp Val 200 205210 Ala Arg Leu Pro Tyr Gln Leu Ser Ile Ser Cys Ala Thr Ser Pro 215 220225 Gly Phe Gln Leu Ser Cys Cys Ile Pro Ser Thr Asn Leu Ala Tyr 230 235240 Thr Ala Ala Trp Ser Pro Gly Glu Gly Ser Lys Ala Ser Ser Phe 245 250255 Asn Glu Ser Gly Ser Gln Cys Phe Val Leu Ala Val Gln Arg Cys 260 265270 Pro Met Ala Asp Thr Thr Tyr Ala Cys Asp Leu Gln Ser Leu Gly 275 280285 Leu Ala Pro Leu Arg Val Pro Ile Ser Ile Thr Ile Ile Gln Asp 290 295300 Gly Asp Ile Thr Cys Pro Glu Asp Ala Ser Val Leu Thr Trp Asn 305 310315 Val Thr Lys Ala Gly His Val Ala Gln Ala Pro Cys Pro Glu Ser 320 325330 Lys Arg Gly Ile Val Arg Arg Leu Cys Gly Ala Asp Gly Val Trp 335 340345 Gly Pro Val His Ser Ser Cys Thr Asp Ala Arg Leu Leu Ala Leu 350 355360 Phe Thr Arg Thr Lys Leu Leu Gln Ala Gly Gln Gly Ser Pro Ala 365 370375 Glu Glu Val Pro Gln Ile Leu Ala Gln Leu Pro Gly Gln Ala Ala 380 385390 Glu Ala Ser Ser Pro Ser Asp Leu Leu Thr Leu Leu Ser Thr Met 395 400405 Lys Tyr Val Ala Lys Val Val Ala Glu Ala Arg Ile Gln Leu Asp 410 415420 Arg Arg Ala Leu Lys Asn Leu Leu Ile Ala Thr Asp Lys Val Leu 425 430435 Asp Met Asp Thr Arg Ser Leu Trp Thr Leu Ala Gln Ala Arg Lys 440 445450 Pro Trp Ala Gly Ser Thr Leu Leu Leu Ala Val Glu Thr Leu Ala 455 460465 Cys Ser Leu Cys Pro Gln Asp His Pro Phe Ala Phe Ser Leu Pro 470 475480 Asn Val Leu Leu Gln Ser Gln Leu Phe Gly Pro Thr Phe Pro Ala 485 490495 Asp Tyr Ser Ile Ser Phe Pro Thr Arg Pro Pro Leu Gln Ala Gln 500 505510 Ile Pro Arg His Ser Leu Ala Pro Leu Val Arg Asn Gly Thr Glu 515 520525 Ile Ser Ile Thr Ser Leu Val Leu Arg Lys Leu Asp His Leu Leu 530 535540 Pro Ser Asn Tyr Gly Gln Gly Leu Gly Asp Ser Leu Tyr Ala Thr 545 550555 Pro Gly Leu Val Leu Val Ile Ser Ile Met Ala Gly Asp Arg Ala 560 565570 Phe Ser Gln Gly Glu Val Ile Met Asp Phe Gly Asn Thr Asp Gly 575 580585 Ser Pro His Cys Val Phe Trp Asp His Ser Leu Phe Gln Gly Arg 590 595600 Gly Gly Trp Ser Lys Glu Gly Cys Gln Ala Gln Val Ala Ser Ala 605 610615 Ser Pro Thr Ala Gln Cys Leu Cys Gln His Leu Thr Ala Phe Ser 620 625630 Val Leu Met Ser Pro His Thr Val Pro Glu Glu Pro Ala Leu Ala 635 640645 Leu Leu Thr Gln Val Gly Leu Gly Ala Ser Ile Leu Ala Leu Leu 650 655660 Val Cys Leu Gly Val Tyr Trp Leu Val Trp Arg Val Val Val Arg 665 670675 Asn Lys Ile Ser Tyr Phe Arg His Ala Ala Leu Leu Asn Met Val 680 685690 Phe Cys Leu Leu Ala Ala Asp Thr Cys Phe Leu Gly Ala Pro Phe 695 700705 Leu Ser Pro Gly Pro Arg Ser Pro Leu Cys Leu Ala Ala Ala Phe 710 715720 Leu Cys His Phe Leu Tyr Leu Ala Thr Phe Phe Trp Met Leu Ala 725 730735 Gln Ala Leu Val Leu Ala His Gln Leu Leu Phe Val Phe His Gln 740 745750 Leu Ala Lys His Arg Val Leu Pro Leu Met Val Leu Leu Gly Tyr 755 760765 Leu Cys Pro Leu Gly Leu Ala Gly Val Thr Leu Gly Leu Tyr Leu 770 775780 Pro Gln Gly Gln Tyr Leu Arg Glu Gly Glu Cys Trp Leu Asp Gly 785 790795 Lys Gly Gly Ala Leu Tyr Thr Phe Val Gly Pro Val Leu Ala Ile 800 805810 Ile Gly Val Asn Gly Leu Val Leu Ala Met Ala Met Leu Lys Leu 815 820825 Leu Arg Pro Ser Leu Ser Glu Gly Pro Pro Ala Glu Lys Arg Gln 830 835840 Ala Leu Leu Gly Val Ile Lys Ala Leu Leu Ile Leu Thr Pro Ile 845 850855 Phe Gly Leu Thr Trp Gly Ala Gly Pro Gly His Ser Val Arg Gly 860 865870 Ser Leu His Gly Pro Ser Leu His Leu His His Ser Gln His Pro 875 880885 Pro Gly Arg Leu His Pro Ile Val Trp Leu Pro His Gly Gln Glu 890 895900 Asp Thr Arg Ser Phe Ala Gln Thr Leu Leu Pro Arg Pro Ser Pro 905 910915 Gln Leu His His Leu Pro Gly His Lys 920 <210> SEQ ID NO 3 <211>LENGTH: 371 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE:<221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:7474936CD1 <400> SEQUENCE: 3 Met Pro Ala Asn Phe Thr Glu Gly Ser Phe AspSer Ser Gly Thr 1 5 10 15 Gly Gln Thr Leu Asp Ser Ser Pro Val Ala CysThr Glu Thr Val 20 25 30 Thr Phe Thr Glu Val Val Glu Gly Lys Glu Trp GlySer Phe Tyr 35 40 45 Tyr Ser Phe Lys Thr Glu Gln Leu Ile Thr Leu Trp ValLeu Phe 50 55 60 Val Phe Thr Ile Val Gly Asn Ser Val Val Leu Phe Ser ThrTrp 65 70 75 Arg Arg Lys Lys Lys Ser Arg Met Thr Phe Phe Val Thr Gln Leu80 85 90 Ala Ile Thr Asp Ser Phe Thr Gly Leu Val Asn Ile Leu Thr Asp 95100 105 Ile Ile Trp Arg Phe Thr Gly Asp Phe Thr Ala Pro Asp Leu Val 110115 120 Cys Arg Val Val Arg Tyr Leu Gln Val Val Leu Leu Tyr Ala Ser 125130 135 Thr Tyr Val Leu Val Ser Leu Ser Ile Asp Arg Tyr His Ala Ile 140145 150 Val Tyr Pro Met Lys Phe Leu Gln Gly Glu Lys Gln Ala Arg Val 155160 165 Leu Ile Val Ile Ala Trp Ser Leu Ser Phe Leu Phe Ser Ile Pro 170175 180 Thr Leu Ile Ile Phe Gly Lys Arg Thr Leu Ser Asn Gly Glu Val 185190 195 Gln Cys Trp Ala Leu Trp Pro Asp Asp Ser Tyr Trp Thr Pro Tyr 200205 210 Met Thr Ile Val Ala Phe Leu Val Tyr Phe Ile Pro Leu Thr Ile 215220 225 Ile Ser Ile Met Tyr Gly Ile Val Ile Arg Thr Ile Trp Ile Lys 230235 240 Ser Lys Thr Tyr Glu Thr Val Ile Ser Asn Cys Ser Asp Gly Lys 245250 255 Leu Cys Ser Ser Tyr Asn Arg Gly Leu Ile Ser Lys Ala Lys Ile 260265 270 Lys Ala Ile Lys Tyr Ser Ile Ile Ile Ile Leu Ala Phe Ile Cys 275280 285 Cys Trp Ser Pro Tyr Phe Leu Phe Asp Ile Leu Asp Asn Phe Asn 290295 300 Leu Leu Pro Asp Thr Gln Glu Arg Phe Tyr Ala Ser Val Ile Ile 305310 315 Gln Asn Leu Pro Ala Leu Asn Ser Ala Ile Asn Pro Leu Ile Tyr 320325 330 Cys Val Phe Ser Ser Ser Ile Ser Phe Pro Cys Arg Glu Arg Arg 335340 345 Ser Gln Asp Ser Arg Met Thr Phe Arg Glu Arg Thr Glu Arg His 350355 360 Glu Met Gln Ile Leu Ser Lys Pro Glu Phe Ile 365 370 <210> SEQ IDNO 4 <211> LENGTH: 313 <212> TYPE: PRT <213> ORGANISM: Homo sapiens<220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION:Incyte ID No: 90012430CD1 <400> SEQUENCE: 4 Met Gln Lys Cys Asp Phe ProSer Met Pro Gly His Asn Thr Ser 1 5 10 15 Arg Asn Ser Ser Cys Asp ProIle Val Thr Pro His Leu Ile Ser 20 25 30 Leu Tyr Phe Ile Val Leu Ile GlyGly Leu Val Gly Val Ile Ser 35 40 45 Ile Leu Phe Leu Leu Val Lys Met AsnThr Arg Ser Val Thr Thr 50 55 60 Met Ala Val Ile Asn Leu Val Val Val HisSer Val Phe Leu Leu 65 70 75 Thr Val Pro Phe Arg Leu Thr Tyr Leu Ile LysLys Thr Trp Met 80 85 90 Phe Gly Leu Pro Phe Cys Lys Phe Val Ser Ala MetLeu His Ile 95 100 105 His Met Tyr Leu Thr Phe Leu Phe Tyr Val Val IleLeu Val Thr 110 115 120 Arg Tyr Leu Ile Phe Phe Lys Cys Lys Asp Lys ValGlu Phe Tyr 125 130 135 Arg Lys Leu His Ala Val Ala Ala Ser Ala Gly MetTrp Thr Leu 140 145 150 Val Ile Val Ile Val Val Pro Leu Val Val Ser ArgTyr Gly Ile 155 160 165 His Glu Glu Tyr Asn Glu Glu His Cys Phe Lys PheHis Lys Glu 170 175 180 Leu Ala Tyr Thr Tyr Val Lys Ile Ile Asn Tyr MetIle Val Ile 185 190 195 Phe Val Ile Ala Val Ala Val Ile Leu Leu Val PheGln Val Phe 200 205 210 Ile Ile Met Leu Met Val Gln Lys Leu Arg His SerLeu Leu Ser 215 220 225 His Gln Glu Phe Trp Ala Gln Leu Lys Asn Leu PhePhe Ile Gly 230 235 240 Val Ile Leu Val Cys Phe Leu Pro Tyr Gln Phe PheArg Ile Tyr 245 250 255 Tyr Leu Asn Val Val Thr His Ser Asn Ala Cys AsnSer Lys Val 260 265 270 Ala Phe Tyr Asn Glu Ile Phe Leu Ser Val Thr AlaIle Ser Cys 275 280 285 Tyr Asp Leu Leu Leu Phe Val Phe Gly Gly Ser HisTrp Phe Lys 290 295 300 Gln Lys Ile Ile Gly Leu Trp Asn Cys Val Leu CysArg 305 310 <210> SEQ ID NO 5 <211> LENGTH: 305 <212> TYPE: PRT <213>ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 90012586CD1 <400> SEQUENCE: 5 Met ProGly His Asn Thr Ser Arg Asn Ser Ser Cys Asp Pro Ile 1 5 10 15 Val ThrPro His Leu Ile Ser Leu Tyr Phe Ile Val Leu Ile Gly 20 25 30 Gly Leu ValGly Val Ile Ser Ile Leu Phe Leu Leu Val Lys Met 35 40 45 Asn Thr Arg SerVal Thr Thr Met Ala Val Ile Asn Leu Val Val 50 55 60 Val His Ser Val PheLeu Leu Thr Val Pro Phe Arg Leu Thr Tyr 65 70 75 Leu Ile Lys Lys Thr TrpMet Phe Gly Leu Pro Phe Cys Lys Phe 80 85 90 Val Ser Ala Met Leu His IleHis Met Tyr Leu Thr Phe Leu Phe 95 100 105 Tyr Val Val Ile Leu Val ThrArg Tyr Leu Ile Phe Phe Lys Cys 110 115 120 Lys Asp Lys Val Glu Phe TyrArg Lys Leu His Ala Val Ala Ala 125 130 135 Ser Ala Gly Met Trp Thr LeuVal Ile Val Ile Val Val Pro Leu 140 145 150 Val Val Ser Arg Tyr Gly IleHis Glu Glu Tyr Asn Glu Glu His 155 160 165 Cys Phe Lys Phe His Lys GluLeu Ala Tyr Thr Tyr Val Lys Ile 170 175 180 Ile Asn Tyr Met Ile Val IlePhe Val Ile Ala Val Ala Val Ile 185 190 195 Leu Leu Val Phe Gln Val PheIle Ile Met Leu Met Val Gln Lys 200 205 210 Leu Arg His Ser Leu Leu SerHis Gln Glu Phe Trp Ala Gln Leu 215 220 225 Lys Asn Leu Phe Phe Ile GlyVal Ile Leu Val Cys Phe Leu Pro 230 235 240 Tyr Gln Phe Phe Arg Ile TyrTyr Leu Asn Val Val Thr His Ser 245 250 255 Asn Ala Cys Asn Ser Lys ValAla Phe Tyr Asn Glu Ile Phe Leu 260 265 270 Ser Val Thr Ala Ile Ser CysTyr Asp Leu Leu Leu Phe Val Phe 275 280 285 Gly Gly Ser His Trp Phe LysGln Lys Ile Ile Gly Leu Trp Asn 290 295 300 Cys Val Leu Cys Arg 305<210> SEQ ID NO 6 <211> LENGTH: 367 <212> TYPE: PRT <213> ORGANISM: Homosapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 90012670CD1 <400> SEQUENCE: 6 Met Val Phe ArgLeu Ile His Gln Ser Ser Glu Ile Ala Cys Lys 1 5 10 15 Asn Gly Leu SerLeu Cys Cys Pro Gly Trp Ser Leu Ala Thr Gln 20 25 30 Ser Trp Leu Thr AspCys Ser Ile Asp Leu Arg Gly Ser Ser Asp 35 40 45 Pro Phe Ile Ser Ala SerSer Val Ala Glu Thr Thr Gly Asp Phe 50 55 60 Pro Ser Met Pro Gly His AsnThr Ser Arg Asn Ser Ser Cys Asp 65 70 75 Pro Ile Val Thr Pro His Leu IleSer Leu Tyr Phe Ile Val Leu 80 85 90 Ile Gly Gly Leu Val Gly Val Ile SerIle Leu Phe Leu Leu Val 95 100 105 Lys Met Asn Thr Arg Ser Val Thr ThrMet Ala Val Ile Asn Leu 110 115 120 Val Val Val His Ser Val Phe Leu LeuThr Val Pro Phe Arg Leu 125 130 135 Thr Tyr Leu Ile Lys Lys Thr Trp MetPhe Gly Leu Pro Phe Cys 140 145 150 Lys Phe Val Ser Ala Met Leu His IleHis Met Tyr Leu Thr Phe 155 160 165 Leu Phe Tyr Val Val Ile Leu Val ThrArg Tyr Leu Ile Phe Phe 170 175 180 Lys Cys Lys Asp Lys Val Glu Phe TyrArg Lys Leu His Ala Val 185 190 195 Ala Ala Ser Ala Gly Met Trp Thr LeuVal Ile Val Ile Val Val 200 205 210 Pro Leu Val Val Ser Arg Tyr Gly IleHis Glu Glu Tyr Asn Glu 215 220 225 Glu His Cys Phe Lys Phe His Lys GluLeu Ala Tyr Thr Tyr Val 230 235 240 Lys Ile Ile Asn Tyr Met Ile Val IlePhe Val Ile Ala Val Ala 245 250 255 Val Ile Leu Leu Val Phe Gln Val PheIle Ile Met Leu Met Val 260 265 270 Gln Lys Leu Arg His Ser Leu Leu SerHis Gln Glu Phe Trp Ala 275 280 285 Gln Leu Lys Asn Leu Phe Phe Ile GlyVal Ile Leu Val Cys Phe 290 295 300 Leu Pro Tyr Gln Phe Phe Arg Ile TyrTyr Leu Asn Val Val Thr 305 310 315 His Ser Asn Ala Cys Asn Ser Lys ValAla Phe Tyr Asn Glu Ile 320 325 330 Phe Leu Ser Val Thr Ala Ile Ser CysTyr Asp Leu Leu Leu Phe 335 340 345 Val Phe Gly Gly Ser His Trp Phe LysGln Lys Ile Ile Gly Leu 350 355 360 Trp Asn Cys Val Leu Cys Arg 365<210> SEQ ID NO 7 <211> LENGTH: 1124 <212> TYPE: PRT <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 2880041CD1 <400> SEQUENCE: 7 Met His Arg TrpVal Lys Glu Lys Asn Ile Thr Val Arg Asp Thr 1 5 10 15 Arg Cys Val TyrPro Lys Ser Leu Gln Ala Gln Pro Val Thr Gly 20 25 30 Val Lys Gln Glu LeuLeu Thr Cys Asp Pro Pro Leu Glu Leu Pro 35 40 45 Ser Phe Tyr Met Thr ProSer His Arg Gln Val Val Phe Glu Gly 50 55 60 Asp Ser Leu Pro Phe Gln CysMet Ala Ser Tyr Ile Asp Gln Asp 65 70 75 Met Gln Val Leu Trp Tyr Gln AspGly Arg Ile Val Glu Thr Asp 80 85 90 Glu Ser Gln Gly Ile Phe Val Glu LysAsn Met Ile His Asn Cys 95 100 105 Ser Leu Ile Ala Ser Ala Leu Thr IleSer Asn Ile Gln Ala Gly 110 115 120 Ser Thr Gly Asn Trp Gly Cys His ValGln Thr Lys Arg Gly Asn 125 130 135 Asn Thr Arg Thr Val Asp Ile Val ValLeu Glu Ser Ser Ala Gln 140 145 150 Tyr Cys Pro Pro Glu Arg Val Val AsnAsn Lys Gly Asp Phe Arg 155 160 165 Trp Pro Arg Thr Leu Ala Gly Ile ThrAla Tyr Leu Gln Cys Thr 170 175 180 Arg Asn Thr His Gly Ser Gly Ile TyrPro Gly Asn Pro Gln Asp 185 190 195 Glu Arg Lys Ala Trp Arg Arg Cys AspArg Gly Gly Phe Trp Ala 200 205 210 Asp Asp Asp Tyr Ser Arg Cys Gln TyrAla Asn Asp Val Thr Arg 215 220 225 Val Leu Tyr Met Phe Asn Gln Met ProLeu Asn Leu Thr Asn Ala 230 235 240 Val Ala Thr Ala Arg Gln Leu Leu AlaTyr Thr Val Glu Ala Ala 245 250 255 Asn Phe Ser Asp Lys Met Asp Val IlePhe Val Ala Glu Met Ile 260 265 270 Glu Lys Phe Gly Arg Phe Thr Lys GluGlu Lys Ser Lys Glu Leu 275 280 285 Gly Asp Val Met Val Asp Ile Ala SerAsn Ile Met Leu Ala Asp 290 295 300 Glu Arg Val Leu Trp Leu Ala Gln ArgGlu Ala Lys Ala Cys Ser 305 310 315 Arg Ile Val Gln Cys Leu Gln Arg IleAla Thr Tyr Arg Leu Ala 320 325 330 Gly Gly Ala His Val Tyr Ser Thr TyrSer Pro Asn Ile Ala Leu 335 340 345 Glu Ala Tyr Val Ile Lys Ser Thr GlyPhe Thr Gly Met Thr Cys 350 355 360 Thr Val Phe Gln Lys Val Ala Ala SerAsp Arg Thr Gly Leu Ser 365 370 375 Asp Tyr Gly Arg Arg Asp Pro Glu GlyAsn Leu Asp Lys Gln Leu 380 385 390 Ser Phe Lys Cys Asn Val Ser Asn ThrPhe Ser Ser Leu Ala Leu 395 400 405 Lys Asn Thr Ile Val Glu Ala Ser IleGln Leu Pro Pro Ser Leu 410 415 420 Phe Ser Pro Lys Gln Lys Arg Glu LeuArg Pro Thr Asp Asp Ser 425 430 435 Leu Tyr Lys Leu Gln Leu Ile Ala PheArg Asn Gly Lys Leu Phe 440 445 450 Pro Ala Thr Gly Asn Ser Thr Asn LeuAla Asp Asp Gly Lys Arg 455 460 465 Arg Thr Val Val Thr Pro Val Ile LeuThr Lys Ile Asp Gly Val 470 475 480 Asn Val Asp Thr His His Ile Pro ValAsn Val Thr Leu Arg Arg 485 490 495 Ile Ala His Gly Ala Asp Ala Val AlaAla Arg Trp Asp Phe Asp 500 505 510 Leu Leu Asn Gly Gln Gly Gly Trp LysSer Asp Gly Cys His Ile 515 520 525 Leu Tyr Ser Asp Glu Asn Ile Thr ThrIle Gln Cys Tyr Ser Leu 530 535 540 Ser Asn Tyr Ala Val Leu Met Asp LeuThr Gly Ser Glu Leu Tyr 545 550 555 Thr Gln Ala Ala Ser Leu Leu His ProVal Val Tyr Thr Thr Ala 560 565 570 Ile Ile Leu Leu Leu Cys Leu Leu AlaVal Ile Val Ser Tyr Ile 575 580 585 Tyr His His Ser Leu Ile Arg Ile SerLeu Lys Ser Trp His Met 590 595 600 Leu Val Asn Leu Cys Phe His Ile PheLeu Thr Cys Val Val Phe 605 610 615 Val Gly Gly Ile Thr Gln Thr Arg AsnAla Ser Ile Cys Gln Ala 620 625 630 Val Gly Ile Ile Leu His Tyr Ser ThrLeu Ala Thr Val Leu Trp 635 640 645 Val Gly Val Thr Ala Arg Asn Ile TyrLys Gln Val Thr Lys Lys 650 655 660 Ala Lys Arg Cys Gln Asp Pro Asp GluPro Pro Pro Pro Pro Arg 665 670 675 Pro Met Leu Arg Phe Tyr Leu Ile GlyGly Gly Ile Pro Ile Ile 680 685 690 Val Cys Gly Ile Thr Ala Ala Ala AsnIle Lys Asn Tyr Gly Ser 695 700 705 Arg Pro Asn Ala Pro Tyr Cys Trp MetAla Trp Glu Pro Ser Leu 710 715 720 Gly Ala Phe Tyr Gly Pro Ala Ser PheIle Thr Phe Val Asn Cys 725 730 735 Met Tyr Phe Leu Ser Ile Phe Ile GlnLeu Lys Arg His Pro Glu 740 745 750 Arg Lys Tyr Glu Leu Lys Glu Pro ThrGlu Glu Gln Gln Arg Leu 755 760 765 Ala Ala Asn Glu Asn Gly Glu Ile AsnHis Gln Asp Ser Met Ser 770 775 780 Leu Ser Leu Ile Ser Thr Ser Ala LeuGlu Asn Glu His Thr Phe 785 790 795 His Ser Gln Leu Leu Gly Ala Ser LeuThr Leu Leu Leu Tyr Val 800 805 810 Ala Leu Trp Met Phe Gly Ala Leu AlaVal Ser Leu Tyr Tyr Pro 815 820 825 Leu Asp Leu Val Phe Ser Phe Val PheGly Ala Thr Ser Leu Ser 830 835 840 Phe Ser Ala Phe Phe Met Val His HisCys Val Asn Arg Glu Asp 845 850 855 Val Arg Leu Ala Trp Ile Met Thr CysCys Pro Gly Arg Ser Ser 860 865 870 Tyr Ser Val Gln Val Asn Val Gln ProPro Asn Ser Asn Gly Thr 875 880 885 Asn Gly Glu Ala Pro Lys Cys Pro AsnSer Ser Ala Glu Ser Ser 890 895 900 Cys Thr Asn Lys Ser Ala Ser Ser PheLys Asn Ser Ser Gln Gly 905 910 915 Cys Lys Leu Thr Asn Leu Gln Ala AlaAla Ala Gln Cys His Ala 920 925 930 Asn Ser Leu Pro Leu Asn Ser Thr ProGln Leu Asp Asn Ser Leu 935 940 945 Thr Glu His Ser Met Asp Asn Asp IleLys Met His Val Ala Pro 950 955 960 Leu Glu Val Gln Phe Arg Thr Asn ValHis Ser Ser Arg His His 965 970 975 Lys Asn Arg Ser Lys Gly His Arg AlaSer Arg Leu Thr Val Leu 980 985 990 Arg Glu Tyr Ala Tyr Asp Val Pro ThrSer Val Glu Gly Ser Val 995 1000 1005 Gln Asn Gly Leu Pro Lys Ser ArgLeu Gly Asn Asn Glu Gly His 1010 1015 1020 Ser Arg Ser Arg Arg Ala TyrLeu Ala Tyr Arg Glu Arg Gln Tyr 1025 1030 1035 Asn Pro Pro Gln Gln AspSer Ser Asp Ala Cys Ser Thr Leu Pro 1040 1045 1050 Lys Ser Ser Arg AsnPhe Glu Lys Pro Val Ser Thr Thr Ser Lys 1055 1060 1065 Lys Asp Ala LeuArg Lys Pro Ala Val Val Glu Leu Glu Asn Gln 1070 1075 1080 Gln Lys SerTyr Gly Leu Asn Leu Ala Ile Gln Asn Gly Pro Ile 1085 1090 1095 Lys SerAsn Gly Gln Glu Gly Pro Leu Leu Gly Thr Asp Ser Thr 1100 1105 1110 GlyAsn Val Arg Thr Gly Leu Trp Lys His Glu Thr Thr Val 1115 1120 <210> SEQID NO 8 <211> LENGTH: 345 <212> TYPE: PRT <213> ORGANISM: Homo sapiens<220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION:Incyte ID No: 90012123CD1 <400> SEQUENCE: 8 Met Tyr Lys Asp Cys Ile GluSer Thr Gly Asp Tyr Phe Leu Leu 1 5 10 15 Cys Asp Ala Glu Gly Pro TrpGly Ile Ile Leu Glu Ser Leu Ala 20 25 30 Ile Leu Gly Ile Val Val Thr IleLeu Leu Leu Leu Ala Phe Leu 35 40 45 Phe Leu Met Arg Lys Ile Gln Asp CysSer Gln Trp Asn Val Leu 50 55 60 Pro Thr Gln Leu Leu Phe Leu Leu Ser ValLeu Gly Leu Phe Gly 65 70 75 Leu Ala Phe Ala Phe Ile Ile Glu Leu Asn GlnGln Thr Ala Pro 80 85 90 Val Arg Tyr Phe Leu Phe Gly Val Leu Phe Ala LeuCys Phe Ser 95 100 105 Cys Leu Leu Ala His Ala Ser Asn Leu Val Lys LeuVal Arg Gly 110 115 120 Cys Val Ser Phe Ser Trp Thr Thr Ile Leu Cys IleAla Ile Gly 125 130 135 Cys Ser Leu Leu Gln Ile Ile Ile Ala Thr Glu TyrVal Thr Leu 140 145 150 Ile Met Thr Arg Gly Met Met Phe Val Asn Met ThrPro Cys Gln 155 160 165 Leu Asn Val Asp Phe Val Val Leu Leu Val Tyr ValLeu Phe Leu 170 175 180 Met Ala Leu Thr Phe Phe Val Ser Lys Ala Thr PheCys Gly Pro 185 190 195 Cys Glu Asn Trp Lys Gln His Gly Arg Leu Ile PheIle Thr Val 200 205 210 Leu Phe Ser Ile Ile Ile Trp Val Val Trp Ile SerMet Leu Leu 215 220 225 Arg Gly Asn Pro Gln Phe Gln Arg Gln Pro Gln TrpAsp Asp Pro 230 235 240 Val Val Cys Ile Ala Leu Val Thr Asn Ala Trp ValPhe Leu Leu 245 250 255 Leu Tyr Ile Val Pro Glu Leu Cys Ile Pro Tyr ArgSer Cys Arg 260 265 270 Gln Glu Cys Pro Leu Gln Gly Asn Ala Cys Pro ValThr Ala Tyr 275 280 285 Gln His Ser Phe Gln Val Glu Asn Gln Glu Leu SerArg Ala Arg 290 295 300 Asp Ser Asp Gly Ala Glu Glu Asp Val Ala Leu ThrSer Tyr Gly 305 310 315 Thr Pro Ile Gln Pro Gln Thr Val Asp Pro Thr GlnGlu Cys Phe 320 325 330 Ile Pro Gln Ala Lys Leu Ser Pro Gln Gln Asp AlaGly Gly Val 335 340 345 <210> SEQ ID NO 9 <211> LENGTH: 300 <212> TYPE:PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY:misc_feature <223> OTHER INFORMATION: Incyte ID No: 90012163CD1 <400>SEQUENCE: 9 Met Tyr Lys Asp Cys Ile Glu Ser Thr Gly Asp Tyr Phe Leu Leu1 5 10 15 Cys Asp Ala Glu Gly Pro Trp Gly Ile Ile Leu Glu Ser Leu Ala 2025 30 Ile Leu Gly Ile Val Val Thr Ile Leu Leu Leu Leu Ala Phe Leu 35 4045 Phe Leu Met Arg Lys Ile Gln Asp Cys Ser Gln Trp Asn Val Leu 50 55 60Pro Thr Gln Leu Leu Phe Leu Leu Ser Val Leu Gly Leu Phe Gly 65 70 75 LeuAla Phe Ala Phe Ile Ile Glu Leu Asn Gln Gln Thr Ala Pro 80 85 90 Val ArgTyr Phe Leu Phe Gly Val Leu Phe Ala Leu Cys Phe Ser 95 100 105 Cys LeuLeu Ala His Ala Ser Asn Leu Val Lys Leu Val Arg Gly 110 115 120 Cys ValSer Phe Ser Trp Thr Thr Ile Leu Cys Ile Ala Ile Gly 125 130 135 Cys SerLeu Leu Gln Ile Ile Ile Ala Thr Glu Tyr Val Thr Leu 140 145 150 Ile MetThr Arg Gly Met Met Phe Val Asn Met Thr Pro Cys Gln 155 160 165 Leu AsnVal Asp Phe Val Val Leu Leu Val Tyr Val Leu Phe Leu 170 175 180 Met AlaLeu Thr Phe Phe Val Ser Lys Ala Thr Phe Cys Gly Pro 185 190 195 Cys GluAsn Trp Lys Gln His Gly Arg Leu Ile Phe Ile Thr Val 200 205 210 Leu PheSer Ile Ile Ile Trp Val Val Trp Ile Ser Met Leu Leu 215 220 225 Arg GlyAsn Pro Gln Phe Gln Arg Gln Pro Gln Trp Asp Asp Pro 230 235 240 Val ValCys Ile Ala Leu Val Thr Asn Ala Trp Val Phe Leu Leu 245 250 255 Leu TyrIle Val Pro Glu Leu Cys Ile Leu Tyr Arg Ser Cys Arg 260 265 270 Gln GluCys Pro Leu Gln Gly Asn Ala Cys Pro Val Thr Ala Tyr 275 280 285 Gln HisSer Phe Gln Val Glu Asn Gln Glu Leu Ser Arg Asp Cys 290 295 300 <210>SEQ ID NO 10 <211> LENGTH: 312 <212> TYPE: PRT <213> ORGANISM: Homosapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7472462CD1 <400> SEQUENCE: 10 Met Pro Ser IleAsn Asp Thr His Phe Tyr Pro Pro Phe Phe Leu 1 5 10 15 Leu Leu Gly IlePro Gly Leu Asp Thr Leu His Ile Trp Ile Ser 20 25 30 Phe Pro Phe Cys IleVal Tyr Leu Ile Ala Ile Val Gly Asn Met 35 40 45 Thr Ile Leu Phe Val IleLys Thr Glu His Ser Leu His Gln Pro 50 55 60 Met Phe Tyr Phe Leu Ala MetLeu Ser Met Ile Asp Leu Gly Leu 65 70 75 Ser Thr Ser Thr Ile Pro Lys MetLeu Gly Ile Phe Trp Phe Asn 80 85 90 Leu Gln Glu Ile Ser Phe Gly Gly CysLeu Leu Gln Met Phe Phe 95 100 105 Ile His Met Phe Thr Gly Met Glu ThrVal Leu Leu Val Val Met 110 115 120 Ala Tyr Asp Arg Phe Val Ala Ile CysAsn Pro Leu Gln Tyr Thr 125 130 135 Met Ile Leu Thr Asn Lys Thr Ile SerIle Leu Ala Ser Val Val 140 145 150 Val Gly Arg Asn Leu Val Leu Val ThrPro Phe Val Phe Leu Ile 155 160 165 Leu Arg Leu Pro Phe Cys Gly His AsnIle Val Pro His Thr Tyr 170 175 180 Cys Glu His Arg Gly Leu Ala Gly LeuAla Cys Ala Pro Ile Lys 185 190 195 Ile Asn Ile Ile Tyr Gly Leu Met ValIle Ser Tyr Ile Ile Val 200 205 210 Asp Val Ile Leu Ile Ala Ser Ser TyrVal Leu Ile Leu Arg Ala 215 220 225 Val Phe Arg Leu Pro Ser Gln Asp ValArg Leu Lys Ala Phe Asn 230 235 240 Thr Cys Gly Ser His Val Cys Val MetLeu Cys Phe Tyr Thr Pro 245 250 255 Ala Phe Phe Ser Phe Met Thr His ArgPhe Gly Gln Asn Ile Pro 260 265 270 His Tyr Ile His Ile Leu Leu Ala AsnLeu Tyr Val Val Val Pro 275 280 285 Pro Ala Leu Asn Pro Val Ile Tyr GlyVal Arg Thr Lys Gln Ile 290 295 300 Arg Glu Gln Ile Val Lys Ile Phe ValGln Lys Glu 305 310 <210> SEQ ID NO 11 <211> LENGTH: 317 <212> TYPE: PRT<213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature<223> OTHER INFORMATION: Incyte ID No: 7474873CD1 <400> SEQUENCE: 11 MetGly Met Val Arg His Thr Asn Glu Ser Asn Leu Ala Gly Phe 1 5 10 15 IleLeu Leu Gly Phe Ser Asp Tyr Pro Gln Leu Gln Lys Val Leu 20 25 30 Phe ValLeu Ile Leu Ile Leu Tyr Leu Leu Thr Ile Leu Gly Asn 35 40 45 Thr Thr IleIle Leu Val Ser Arg Leu Glu Pro Lys Leu His Met 50 55 60 Pro Met Tyr PhePhe Leu Ser His Leu Ser Phe Leu Tyr Arg Cys 65 70 75 Phe Thr Ser Ser ValIle Pro Gln Leu Leu Val Asn Leu Trp Glu 80 85 90 Pro Met Lys Thr Ile AlaTyr Gly Gly Cys Leu Val His Leu Tyr 95 100 105 Asn Ser His Ala Leu GlySer Thr Glu Cys Val Leu Pro Ala Val 110 115 120 Met Ser Cys Asp Arg TyrVal Ala Val Cys Arg Pro Leu His Tyr 125 130 135 Thr Val Leu Met His IleHis Leu Cys Met Ala Leu Ala Ser Met 140 145 150 Ala Trp Leu Ser Gly IleAla Thr Thr Leu Val Gln Ser Thr Leu 155 160 165 Thr Leu Gln Leu Pro PheCys Gly His Arg Gln Val Asp His Phe 170 175 180 Ile Cys Glu Val Pro ValLeu Ile Lys Leu Ala Cys Val Gly Thr 185 190 195 Thr Phe Asn Glu Ala GluLeu Phe Val Ala Ser Ile Leu Phe Leu 200 205 210 Ile Val Pro Val Ser PheIle Leu Val Ser Ser Gly Tyr Ile Ala 215 220 225 His Ala Val Leu Arg IleLys Ser Ala Thr Arg Arg Gln Lys Ala 230 235 240 Phe Gly Thr Cys Phe SerHis Leu Thr Val Val Thr Ile Phe Tyr 245 250 255 Gly Thr Ile Ile Phe MetTyr Leu Gln Pro Ala Lys Ser Arg Ser 260 265 270 Arg Asp Gln Gly Lys PheVal Ser Leu Phe Tyr Thr Val Val Thr 275 280 285 Arg Met Leu Asn Pro LeuIle Tyr Thr Leu Arg Ile Lys Glu Val 290 295 300 Lys Gly Ala Leu Lys LysVal Leu Ala Lys Ala Leu Gly Val Asn 305 310 315 Ile Leu <210> SEQ ID NO12 <211> LENGTH: 309 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 7475172CD1 <400> SEQUENCE: 12 Met Ala Ala Gly Asn His Ser Thr ValThr Glu Phe Ile Leu Lys 1 5 10 15 Gly Leu Thr Lys Arg Ala Asp Leu GlnLeu Pro Leu Phe Leu Leu 20 25 30 Phe Leu Gly Ile Tyr Leu Val Thr Ile ValGly Asn Leu Gly Met 35 40 45 Ile Thr Leu Ile Cys Leu Asn Ser Gln Leu HisThr Pro Met Tyr 50 55 60 Tyr Phe Leu Ser Asn Leu Ser Leu Met Asp Leu CysTyr Ser Ser 65 70 75 Val Ile Thr Pro Lys Met Leu Val Asn Phe Val Ser GluLys Asn 80 85 90 Ile Ile Ser Tyr Ala Gly Cys Met Ser Gln Leu Tyr Phe PheLeu 95 100 105 Val Phe Val Ile Ala Glu Cys Tyr Met Leu Thr Val Met AlaTyr 110 115 120 Asp Arg Tyr Val Ala Ile Cys His Pro Leu Leu Tyr Asn IleIle 125 130 135 Met Ser His His Thr Cys Leu Leu Leu Val Ala Val Val TyrAla 140 145 150 Ile Gly Leu Ile Gly Ser Thr Ile Glu Thr Gly Leu Met LeuLys 155 160 165 Leu Pro Tyr Cys Glu His Leu Ile Ser His Tyr Phe Cys AspIle 170 175 180 Leu Pro Leu Met Lys Leu Ser Cys Ser Ser Thr Tyr Asp ValGlu 185 190 195 Met Thr Val Phe Phe Ser Ala Gly Phe Asn Ile Ile Val ThrSer 200 205 210 Leu Thr Val Leu Val Ser Tyr Thr Phe Ile Leu Ser Ser IleLeu 215 220 225 Gly Ile Ser Thr Thr Glu Gly Arg Ser Lys Ala Phe Ser ThrCys 230 235 240 Ser Ser His Leu Ala Ala Val Gly Met Phe Tyr Gly Ser ThrAla 245 250 255 Phe Met Tyr Leu Lys Pro Ser Thr Ile Ser Ser Leu Thr GlnGlu 260 265 270 Asn Val Ala Ser Val Phe Tyr Thr Thr Val Ile Pro Met LeuAsn 275 280 285 Pro Leu Ile Tyr Ser Leu Arg Asn Lys Glu Val Lys Ala AlaVal 290 295 300 Gln Lys Thr Leu Arg Gly Lys Leu Phe 305 <210> SEQ ID NO13 <211> LENGTH: 343 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 7475259CD1 <400> SEQUENCE: 13 Met Lys Gln Tyr Ser Val Gly Asn GlnHis Ser Asn Tyr Arg Ser 1 5 10 15 Leu Leu Phe Pro Phe Leu Cys Ser GlnMet Thr Gln Leu Thr Ala 20 25 30 Ser Gly Asn Gln Thr Met Val Thr Glu PheLeu Phe Ser Met Phe 35 40 45 Pro His Ala His Arg Gly Gly Leu Leu Phe PheIle Pro Leu Leu 50 55 60 Leu Ile Tyr Gly Phe Ile Leu Thr Gly Asn Leu IleMet Phe Ile 65 70 75 Val Ile Gln Val Gly Met Ala Leu His Thr Pro Leu TyrPhe Phe 80 85 90 Ile Ser Val Leu Ser Phe Leu Glu Ile Cys Tyr Thr Thr ThrThr 95 100 105 Ile Pro Lys Met Leu Ser Cys Leu Ile Ser Glu Gln Lys SerIle 110 115 120 Ser Val Ala Gly Cys Leu Leu Gln Met Tyr Phe Phe His SerLeu 125 130 135 Gly Ile Thr Glu Ser Cys Val Leu Thr Ala Met Ala Ile AspArg 140 145 150 Tyr Ile Ala Ile Cys Asn Pro Leu Arg Tyr Pro Thr Ile MetIle 155 160 165 Pro Lys Leu Cys Ile Gln Leu Thr Val Gly Ser Cys Phe CysGly 170 175 180 Phe Leu Leu Val Leu Pro Glu Ile Ala Trp Ile Ser Thr LeuPro 185 190 195 Phe Cys Gly Ser Asn Gln Ile His Gln Ile Phe Cys Asp PheThr 200 205 210 Pro Val Leu Ser Leu Ala Cys Thr Asp Thr Phe Leu Val ValIle 215 220 225 Val Asp Ala Ile His Ala Ala Glu Ile Val Ala Ser Phe LeuVal 230 235 240 Ile Ala Leu Ser Tyr Ile Arg Ile Ile Ile Val Ile Leu GlyMet 245 250 255 His Ser Ala Glu Gly His His Lys Ala Phe Ser Thr Cys AlaAla 260 265 270 His Leu Ala Val Phe Leu Leu Phe Phe Gly Ser Val Ala ValMet 275 280 285 Tyr Leu Arg Phe Ser Ala Thr Tyr Ser Val Phe Trp Asp ThrAla 290 295 300 Ile Ala Val Thr Phe Val Ile Leu Ala Pro Phe Phe Asn ProIle 305 310 315 Ile Tyr Ser Leu Lys Asn Lys Asp Met Lys Glu Ala Ile GlyArg 320 325 330 Leu Phe His Tyr Gln Lys Arg Ala Gly Trp Ala Gly Lys 335340 <210> SEQ ID NO 14 <211> LENGTH: 311 <212> TYPE: PRT <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7475267CD1 <400> SEQUENCE: 14 Met Asp His HisMet Pro Pro Asn Asn Val Thr Glu Phe Ile Leu 1 5 10 15 Leu Gly Leu ThrGln Asn Pro His Leu Gln Lys Ile Leu Phe Ile 20 25 30 Val Phe Leu Phe IlePhe Leu Phe Thr Met Leu Ala Asn Leu Phe 35 40 45 Ile Val Ile Thr Ile SerCys Ser Pro Thr Leu Ser Ser Pro Met 50 55 60 Tyr Phe Phe Leu Thr Tyr LeuSer Phe Ile Asp Ala Ser Tyr Thr 65 70 75 Ser Val Thr Thr Pro Lys Met IleThr Asp Leu Leu Tyr Gln Arg 80 85 90 Arg Thr Ile Ser Leu Ala Gly Cys LeuThr Gln Leu Phe Val Glu 95 100 105 His Leu Leu Gly Gly Ser Glu Ile IleLeu Leu Ile Val Met Ala 110 115 120 Tyr Asp Arg Tyr Val Ala Ile Cys LysPro Leu His Tyr Thr Thr 125 130 135 Ile Met Gln Gln Gly Ile Cys His LeuLeu Val Val Ile Ala Trp 140 145 150 Ile Gly Gly Ile Leu His Ala Thr ValGln Ile Leu Phe Met Thr 155 160 165 Asp Leu Pro Phe Cys Gly Pro Asn ValIle Asp His Phe Met Cys 170 175 180 Asp Leu Phe Pro Leu Leu Lys Leu AlaCys Arg Asp Thr Tyr Arg 185 190 195 Leu Gly Met Leu Val Ala Ala Asn SerGly Ala Met Cys Leu Leu 200 205 210 Ile Phe Ser Leu Leu Val Ile Ser TyrIle Val Ile Leu Ser Ser 215 220 225 Leu Lys Ser Tyr Ser Ser Glu Gly GlnHis Lys Ala Leu Ser Thr 230 235 240 Cys Gly Ser His Phe Thr Val Val ValLeu Phe Phe Val Pro Cys 245 250 255 Ile Phe Thr Tyr Met His Pro Val ValThr Tyr Ser Val Asp Lys 260 265 270 Leu Val Thr Val Phe Phe Ala Ile LeuThr Pro Met Leu Asn Pro 275 280 285 Ile Ile Tyr Thr Val Arg Asn Thr GluVal Lys Asn Ala Val Arg 290 295 300 Ser Leu Leu Arg Lys Arg Val Thr ValTyr Ala 305 310 <210> SEQ ID NO 15 <211> LENGTH: 307 <212> TYPE: PRT<213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature<223> OTHER INFORMATION: Incyte ID No: 7475271CD1 <400> SEQUENCE: 15 MetAsn His Ser Val Val Thr Glu Phe Ile Ile Leu Gly Leu Thr 1 5 10 15 LysLys Pro Glu Leu Gln Gly Ile Ile Phe Leu Phe Phe Leu Ile 20 25 30 Val TyrLeu Val Ala Phe Leu Gly Asn Met Leu Ile Ile Ile Ala 35 40 45 Lys Ile TyrAsn Asn Thr Leu His Thr Pro Met Tyr Val Phe Leu 50 55 60 Leu Thr Leu AlaVal Val Asp Ile Ile Cys Thr Thr Ser Ile Ile 65 70 75 Pro Lys Met Leu GlyThr Met Leu Thr Ser Glu Asn Thr Ile Ser 80 85 90 Tyr Ala Gly Cys Met SerGln Leu Phe Leu Phe Thr Trp Ser Leu 95 100 105 Gly Ala Glu Met Val LeuPhe Thr Thr Met Ala Tyr Asp Arg Tyr 110 115 120 Val Ala Ile Cys Phe ProLeu His Tyr Ser Thr Ile Met Asn His 125 130 135 His Met Cys Val Ala LeuLeu Ser Met Val Met Ala Ile Ala Val 140 145 150 Thr Asn Ser Trp Val HisThr Ala Leu Ile Met Arg Leu Thr Phe 155 160 165 Cys Gly Pro Asn Thr IleAsp His Phe Phe Cys Glu Ile Pro Pro 170 175 180 Leu Leu Ala Leu Ser CysSer Pro Val Arg Ile Asn Glu Val Met 185 190 195 Val Tyr Val Ala Asp IleThr Leu Ala Ile Gly Asp Phe Ile Leu 200 205 210 Thr Cys Ile Ser Tyr GlyPhe Ile Ile Val Ala Ile Leu Arg Ile 215 220 225 Arg Thr Val Glu Gly LysArg Lys Ala Phe Ser Thr Cys Ser Ser 230 235 240 His Leu Thr Val Val ThrLeu Tyr Tyr Ser Pro Val Ile Tyr Thr 245 250 255 Tyr Ile Arg Pro Ala SerSer Tyr Thr Phe Glu Arg Asp Lys Val 260 265 270 Val Ala Ala Leu Tyr ThrLeu Val Thr Pro Thr Leu Asn Pro Met 275 280 285 Val Tyr Ser Phe Gln AsnArg Glu Met Gln Ala Gly Ile Arg Lys 290 295 300 Val Phe Ala Phe Leu LysHis 305 <210> SEQ ID NO 16 <211> LENGTH: 316 <212> TYPE: PRT <213>ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 7475305CD1 <400> SEQUENCE: 16 Met LysIle Ala Asn Asn Thr Val Val Thr Glu Phe Ile Leu Leu 1 5 10 15 Gly LeuThr Gln Ser Gln Asp Ile Gln Leu Leu Val Phe Val Leu 20 25 30 Ile Leu IlePhe Tyr Leu Ile Ile Leu Pro Gly Asn Phe Leu Ile 35 40 45 Ile Phe Thr IleArg Ser Asp Pro Gly Leu Thr Ala Pro Leu Tyr 50 55 60 Leu Phe Leu Gly AsnLeu Ala Phe Leu Asp Ala Ser Tyr Ser Phe 65 70 75 Ile Val Ala Pro Arg MetLeu Val Asp Phe Leu Ser Glu Lys Lys 80 85 90 Val Ile Ser Tyr Arg Gly CysIle Thr Gln Leu Phe Phe Leu His 95 100 105 Phe Leu Gly Gly Gly Glu GlyLeu Leu Leu Val Val Met Ala Phe 110 115 120 Asp Arg Tyr Ile Ala Ile CysArg Pro Leu His Cys Ser Thr Val 125 130 135 Met Asn Pro Arg Ala Cys TyrAla Met Met Leu Ala Leu Trp Leu 140 145 150 Gly Gly Phe Val His Ser IleIle Gln Val Val Leu Ile Leu Arg 155 160 165 Leu Pro Phe Cys Gly Pro AsnGln Leu Asp Asn Phe Phe Cys Asp 170 175 180 Val Arg Gln Val Ile Lys LeuAla Cys Thr Asp Met Phe Val Val 185 190 195 Glu Leu Leu Met Val Phe AsnSer Gly Leu Met Thr Leu Leu Cys 200 205 210 Phe Leu Gly Leu Leu Ala SerTyr Ala Val Ile Leu Cys His Val 215 220 225 Arg Arg Ala Ala Ser Glu GlyLys Asn Lys Ala Met Ser Thr Cys 230 235 240 Thr Thr Arg Val Ile Ile IleLeu Leu Met Phe Gly Pro Ala Ile 245 250 255 Phe Ile Tyr Met Cys Pro PheArg Ala Leu Pro Ala Asp Lys Met 260 265 270 Val Ser Leu Phe His Thr ValIle Phe Pro Leu Met Asn Pro Met 275 280 285 Ile Tyr Thr Leu Arg Asn GlnGlu Val Lys Thr Ser Met Lys Arg 290 295 300 Leu Leu Ser Arg His Val ValCys Gln Val Asp Phe Ile Ile Arg 305 310 315 Asn <210> SEQ ID NO 17 <211>LENGTH: 317 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE:<221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:7476160CD1 <400> SEQUENCE: 17 Met Met Arg Leu Met Lys Glu Val Arg GlyArg Asn Gln Thr Glu 1 5 10 15 Val Thr Glu Phe Leu Leu Leu Gly Leu SerAsp Asn Pro Asp Leu 20 25 30 Gln Gly Val Leu Phe Ala Leu Phe Leu Leu IleTyr Met Ala Asn 35 40 45 Met Val Gly Asn Leu Gly Met Ile Val Leu Ile LysIle Asp Leu 50 55 60 Cys Leu His Thr Pro Met Tyr Phe Phe Leu Ser Ser LeuSer Phe 65 70 75 Val Asp Ala Ser Tyr Ser Ser Ser Val Thr Pro Lys Met LeuVal 80 85 90 Asn Leu Met Ala Glu Asn Lys Ala Ile Ser Phe His Gly Cys Ala95 100 105 Ala Gln Phe Tyr Phe Phe Gly Ser Phe Leu Gly Thr Glu Cys Phe110 115 120 Leu Leu Ala Met Met Ala Tyr Asp Arg Tyr Ala Ala Ile Trp Asn125 130 135 Pro Leu Leu Tyr Pro Val Leu Val Ser Gly Arg Ile Cys Phe Leu140 145 150 Leu Ile Ala Thr Ser Phe Leu Ala Gly Cys Gly Asn Ala Ala Ile155 160 165 His Thr Gly Met Thr Phe Arg Leu Ser Phe Cys Gly Ser Asn Arg170 175 180 Ile Asn His Phe Tyr Cys Asp Thr Pro Pro Leu Leu Lys Leu Ser185 190 195 Cys Ser Asp Thr His Phe Asn Gly Ile Val Ile Met Ala Phe Ser200 205 210 Ser Phe Ile Val Ile Ser Cys Val Met Ile Val Leu Ile Ser Tyr215 220 225 Leu Cys Ile Phe Ile Ala Val Leu Lys Met Pro Ser Leu Glu Gly230 235 240 Arg His Lys Ala Phe Ser Thr Cys Ala Ser Tyr Leu Met Ala Val245 250 255 Thr Ile Phe Phe Gly Thr Ile Leu Phe Met Tyr Leu Arg Pro Thr260 265 270 Ser Ser Tyr Ser Met Glu Gln Asp Lys Val Val Ser Val Phe Tyr275 280 285 Thr Val Ile Ile Pro Val Leu Asn Pro Leu Ile Tyr Ser Leu Lys290 295 300 Asn Lys Asp Val Lys Lys Ala Leu Lys Lys Ile Leu Trp Lys His305 310 315 Ile Leu <210> SEQ ID NO 18 <211> LENGTH: 317 <212> TYPE: PRT<213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature<223> OTHER INFORMATION: Incyte ID No: 7476781CD1 <400> SEQUENCE: 18 MetGly Asp Asn Gln Ser Arg Val Thr Glu Phe Ile Leu Val Gly 1 5 10 15 PheGln Leu Ser Val Glu Met Glu Val Leu Leu Phe Trp Ile Phe 20 25 30 Ser LeuLeu Tyr Leu Phe Ser Leu Leu Gly Asn Gly Val Ile Phe 35 40 45 Gly Leu IleCys Leu Asp Ser Lys Leu His Thr Pro Met Tyr Phe 50 55 60 Phe Leu Ser HisLeu Ala Val Ile Asp Met Ser Tyr Ala Ser Asn 65 70 75 Asn Val Pro Lys MetLeu Ala Asn Leu Val Asn Gln Lys Arg Thr 80 85 90 Ile Ser Phe Ile Ser CysIle Met Gln Thr Phe Leu Tyr Leu Ala 95 100 105 Phe Ala Val Thr Val CysLeu Ile Leu Val Val Met Ser Tyr Asp 110 115 120 Arg Phe Val Ala Ile CysHis Pro Leu His Tyr Thr Val Ile Met 125 130 135 Ser Trp Arg Val Cys ThrVal Leu Ala Val Ala Ser Trp Val Phe 140 145 150 Ser Phe Leu Leu Ala LeuVal His Leu Val Leu Ile Leu Arg Leu 155 160 165 Pro Phe Cys Gly Pro GlnGlu Val Asn His Phe Phe Gly Glu Ile 170 175 180 Leu Ser Val Leu Lys LeuAla Cys Ala Asp Thr Trp Leu Asn Gln 185 190 195 Val Val Ile Phe Ala AlaCys Met Phe Ile Leu Val Gly Pro Leu 200 205 210 Cys Leu Val Leu Val SerTyr Leu His Ile Leu Ala Ala Ile Leu 215 220 225 Arg Ile Gln Ser Gly GluGly Arg Arg Lys Ala Phe Ser Thr Cys 230 235 240 Ser Ser His Leu Cys ValVal Gly Leu Phe Phe Gly Ser Ala Ile 245 250 255 Val Met Tyr Met Ala ProLys Ser Ser His Ser Gln Glu Arg Arg 260 265 270 Lys Ile Leu Ser Leu PheTyr Ser Leu Phe Asn Pro Ile Leu Asn 275 280 285 Pro Leu Ile Tyr Ser LeuArg Asn Ala Glu Val Lys Gly Ala Leu 290 295 300 Lys Arg Val Leu Trp LysGln Arg Ser Ile Glu Glu Ser Phe Glu 305 310 315 Ile Ser <210> SEQ ID NO19 <211> LENGTH: 319 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 7487603CD1 <400> SEQUENCE: 19 Met Phe Pro Ala Asn Trp Thr Ser ValLys Val Phe Phe Phe Leu 1 5 10 15 Gly Phe Phe His Tyr Pro Lys Val GlnVal Ile Ile Phe Ala Val 20 25 30 Cys Leu Leu Met Tyr Leu Ile Thr Leu LeuGly Asn Ile Phe Leu 35 40 45 Ile Ser Ile Thr Ile Leu Asp Ser His Leu HisThr Pro Met Tyr 50 55 60 Leu Phe Leu Ser Asn Leu Ser Phe Leu Asp Ile TrpTyr Ser Ser 65 70 75 Ser Ala Leu Ser Pro Met Leu Ala Asn Phe Val Ser GlyArg Asn 80 85 90 Thr Ile Ser Phe Ser Gly Cys Ala Thr Gln Met Tyr Leu SerLeu 95 100 105 Ala Met Gly Ser Thr Glu Cys Val Leu Leu Pro Met Met AlaTyr 110 115 120 Asp Arg Tyr Val Ala Ile Cys Asn Pro Leu Arg Tyr Pro ValIle 125 130 135 Met Asn Arg Arg Thr Cys Val Gln Ile Ala Ala Gly Ser TrpMet 140 145 150 Thr Gly Cys Leu Thr Ala Met Val Glu Met Met Ser Val LeuPro 155 160 165 Leu Ser Leu Cys Gly Asn Ser Ile Ile Asn His Phe Thr CysGlu 170 175 180 Ile Leu Ala Ile Leu Lys Leu Val Cys Val Asp Thr Ser LeuVal 185 190 195 Gln Leu Ile Met Leu Val Ile Ser Val Leu Leu Leu Pro MetPro 200 205 210 Met Leu Leu Ile Cys Ile Ser Tyr Ala Phe Ile Leu Ala SerIle 215 220 225 Leu Arg Ile Ser Ser Val Glu Gly Arg Ser Lys Ala Phe SerThr 230 235 240 Cys Thr Ala His Leu Met Val Val Val Leu Phe Tyr Gly ThrAla 245 250 255 Leu Ser Met His Leu Lys Pro Ser Ala Val Asp Ser Gln GluIle 260 265 270 Asp Lys Phe Met Ala Leu Val Tyr Ala Gly Gln Thr Pro MetLeu 275 280 285 Asn Pro Ile Ile Tyr Ser Leu Arg Asn Lys Glu Val Lys ValAla 290 295 300 Leu Lys Lys Leu Leu Ile Arg Asn His Phe Asn Thr Ala PheIle 305 310 315 Ser Ile Leu Lys <210> SEQ ID NO 20 <211> LENGTH: 318<212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:58015601CD1 <400> SEQUENCE: 20 Met Glu Gly Asn Gln Thr Trp Ile Thr AspIle Thr Leu Leu Gly 1 5 10 15 Phe Gln Ala Gly Pro Ala Leu Ala Ile LeuLeu Cys Gly Leu Phe 20 25 30 Ser Val Phe Tyr Thr Leu Thr Leu Leu Gly AsnGly Val Ile Phe 35 40 45 Gly Ile Ile Cys Leu Asp Ser Lys Leu His Thr ProMet Tyr Phe 50 55 60 Phe Leu Ser His Leu Ala Ile Ile Asp Met Ser Tyr AlaSer Asn 65 70 75 Asn Val Pro Lys Met Leu Ala Asn Leu Met Asn Gln Lys ArgThr 80 85 90 Ile Ser Phe Val Pro Cys Ile Met Gln Thr Phe Leu Tyr Leu Ala95 100 105 Phe Ala Val Thr Glu Cys Leu Ile Leu Val Val Met Ser Tyr Asp110 115 120 Arg Tyr Val Ala Ile Cys His Pro Phe Gln Tyr Thr Val Ile Met125 130 135 Ser Trp Arg Val Cys Thr Ile Leu Val Leu Thr Ser Trp Ser Cys140 145 150 Gly Phe Ala Leu Ser Leu Val His Glu Ile Leu Leu Leu Arg Leu155 160 165 Pro Phe Cys Gly Pro Arg Asp Val Asn His Leu Phe Cys Glu Ile170 175 180 Leu Ser Val Leu Lys Leu Ala Cys Ala Asp Thr Trp Val Asn Gln185 190 195 Val Val Ile Phe Ala Thr Cys Val Phe Val Leu Val Gly Pro Leu200 205 210 Ser Leu Ile Leu Val Ser Tyr Met His Ile Leu Gly Ala Ile Leu215 220 225 Lys Ile Gln Thr Lys Glu Gly Arg Ile Lys Ala Phe Ser Thr Cys230 235 240 Ser Ser His Leu Cys Val Val Gly Leu Phe Phe Gly Ile Ala Met245 250 255 Val Val Tyr Met Val Pro Asp Ser Asn Gln Arg Glu Glu Gln Glu260 265 270 Lys Met Leu Ser Leu Phe His Ser Val Leu Asn Pro Met Leu Asn275 280 285 Pro Leu Ile Tyr Ser Leu Arg Asn Ala Gln Leu Lys Gly Ala Leu290 295 300 His Arg Ala Leu Gln Arg Lys Arg Ser Met Arg Thr Val Tyr Gly305 310 315 Leu Cys Leu <210> SEQ ID NO 21 <211> LENGTH: 351 <212> TYPE:PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY:misc_feature <223> OTHER INFORMATION: Incyte ID No: 6541249CD1 <400>SEQUENCE: 21 Met Ser Gly Asp Asn Ser Ser Ser Leu Thr Pro Gly Phe Phe Ile1 5 10 15 Leu Asn Gly Val Pro Gly Leu Glu Ala Thr His Ile Trp Ile Ser 2025 30 Leu Pro Phe Cys Phe Met Tyr Ile Ile Ala Val Val Gly Asn Cys 35 4045 Gly Leu Ile Cys Leu Ile Ser His Glu Glu Ala Leu His Arg Pro 50 55 60Met Tyr Tyr Phe Leu Ala Leu Leu Ser Phe Thr Asp Val Thr Leu 65 70 75 CysThr Thr Met Val Pro Asn Met Leu Cys Ile Phe Trp Phe Asn 80 85 90 Leu LysGlu Ile Asp Phe Asn Ala Cys Leu Ala Gln Met Phe Phe 95 100 105 Val HisMet Leu Thr Gly Met Glu Ser Gly Val Leu Met Leu Met 110 115 120 Ala LeuAsp Arg Tyr Val Ala Ile Cys Tyr Pro Leu Arg Tyr Ala 125 130 135 Thr IleLeu Thr Asn Pro Val Ile Ala Lys Ala Gly Leu Ala Thr 140 145 150 Phe LeuArg Asn Val Met Leu Ile Ile Pro Phe Thr Leu Leu Thr 155 160 165 Lys ArgLeu Pro Tyr Cys Arg Gly Asn Phe Ile Pro His Thr Tyr 170 175 180 Cys AspHis Met Ser Val Ala Lys Val Ser Cys Gly Asn Phe Lys 185 190 195 Val AsnAla Ile Tyr Gly Leu Met Val Ala Leu Leu Ile Gly Val 200 205 210 Phe AspIle Cys Cys Ile Ser Val Ser Tyr Thr Met Ile Leu Gln 215 220 225 Ala ValMet Ser Leu Ser Ser Ala Asp Ala Arg His Lys Ala Phe 230 235 240 Ser ThrCys Thr Ser His Met Cys Ser Ile Val Ile Thr Tyr Val 245 250 255 Ala AlaPhe Phe Thr Phe Phe Thr His Arg Phe Val Gly His Asn 260 265 270 Ile ProAsn His Ile His Ile Ile Val Ala Asn Leu Tyr Leu Leu 275 280 285 Leu ProPro Thr Met Asn Pro Ile Val Tyr Gly Val Lys Thr Lys 290 295 300 Gln IleGln Glu Gly Val Ile Lys Phe Leu Leu Gly Asp Lys Lys 305 310 315 Asn ValGln Gly Phe Cys Phe Ser Gln Val Ile Ser Leu Gly Ser 320 325 330 Pro PheLys Met Asp Leu Asn Gly Asn Asn Arg Leu Gln Val Leu 335 340 345 Arg LysGlu Arg Glu Glu 350 <210> SEQ ID NO 22 <211> LENGTH: 315 <212> TYPE: PRT<213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature<223> OTHER INFORMATION: Incyte ID No: 7472078CD1 <400> SEQUENCE: 22 MetGlu Ser Gly Asn Gln Ser Thr Val Thr Glu Phe Ile Phe Thr 1 5 10 15 GlyPhe Pro Gln Leu Gln Asp Gly Ser Leu Leu Tyr Phe Phe Pro 20 25 30 Leu LeuPhe Ile Tyr Thr Phe Ile Ile Ile Asp Asn Leu Leu Ile 35 40 45 Phe Ser AlaVal Arg Leu Asp Thr His Leu His Asn Pro Met Tyr 50 55 60 Asn Phe Ile SerIle Phe Ser Phe Leu Glu Ile Trp Tyr Thr Thr 65 70 75 Ala Thr Ile Pro LysMet Leu Ser Asn Leu Ile Ser Glu Lys Lys 80 85 90 Ala Ile Ser Met Thr GlyCys Ile Leu Gln Met Tyr Phe Phe His 95 100 105 Ser Leu Glu Asn Ser GluGly Ile Leu Leu Thr Thr Met Ala Ile 110 115 120 Asp Arg Tyr Val Ala IleCys Asn Pro Leu Arg Tyr Gln Met Ile 125 130 135 Met Thr Pro Arg Leu CysAla Gln Leu Ser Ala Gly Ser Cys Leu 140 145 150 Phe Gly Phe Leu Ile LeuLeu Pro Glu Ile Val Met Ile Ser Thr 155 160 165 Leu Pro Phe Cys Gly ProAsn Gln Ile His Gln Ile Phe Cys Asp 170 175 180 Leu Val Pro Val Leu SerLeu Ala Cys Thr Asp Thr Ser Met Ile 185 190 195 Leu Ile Glu Asp Val IleHis Ala Val Thr Ile Ile Ile Thr Phe 200 205 210 Leu Ile Ile Ala Leu SerTyr Val Arg Ile Val Thr Val Ile Leu 215 220 225 Arg Ile Ser Ser Ser GluGly Arg Gln Lys Ala Phe Ser Thr Cys 230 235 240 Ala Gly His Leu Met ValPhe Leu Ile Phe Phe Gly Ser Val Ser 245 250 255 Leu Met Tyr Leu Arg PheSer Asp Thr Tyr Pro Pro Val Leu Asp 260 265 270 Thr Ala Ile Ala Leu MetPhe Thr Val Leu Ala Pro Phe Phe Asn 275 280 285 Pro Ile Ile Tyr Ser LeuArg Asn Lys Asp Met Asn Asn Ala Ile 290 295 300 Lys Lys Leu Phe Cys LeuGln Lys Val Leu Asn Lys Pro Gly Gly 305 310 315 <210> SEQ ID NO 23 <211>LENGTH: 312 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE:<221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:7472087CD1 <400> SEQUENCE: 23 Met Ser Val Leu Asn Asn Ser Glu Val LysLeu Phe Leu Leu Ile 1 5 10 15 Gly Ile Pro Gly Leu Glu His Ala His IleTrp Phe Ser Ile Pro 20 25 30 Ile Cys Leu Met Tyr Leu Leu Ala Ile Met GlyAsn Cys Thr Ile 35 40 45 Leu Phe Ile Ile Lys Thr Glu Pro Ser Leu His GluPro Met Tyr 50 55 60 Tyr Phe Leu Ala Met Leu Ala Val Ser Asp Met Gly LeuSer Leu 65 70 75 Ser Ser Leu Pro Thr Met Leu Arg Val Phe Leu Phe Asn AlaMet 80 85 90 Gly Ile Ser Pro Asn Ala Cys Phe Ala Gln Glu Phe Phe Ile His95 100 105 Gly Phe Thr Val Met Glu Ser Ser Val Leu Leu Ile Met Ser Leu110 115 120 Asp Arg Phe Leu Ala Ile His Asn Pro Leu Arg Tyr Ser Ser Ile125 130 135 Leu Thr Ser Asn Arg Val Ala Lys Met Gly Leu Ile Leu Ala Ile140 145 150 Arg Ser Ile Leu Leu Val Ile Pro Phe Pro Phe Thr Leu Arg Arg155 160 165 Leu Lys Tyr Cys Gln Lys Asn Leu Leu Ser His Ser Tyr Cys Leu170 175 180 His Gln Asp Thr Met Lys Leu Ala Cys Ser Asp Asn Lys Thr Asn185 190 195 Val Ile Tyr Gly Phe Phe Ile Ala Leu Cys Thr Met Leu Asp Leu200 205 210 Ala Leu Ile Val Leu Ser Tyr Val Leu Ile Leu Lys Thr Ile Leu215 220 225 Ser Ile Ala Ser Leu Ala Glu Arg Leu Lys Ala Leu Asn Thr Cys230 235 240 Val Ser His Ile Cys Ala Val Leu Thr Phe Tyr Val Pro Ile Ile245 250 255 Thr Leu Ala Ala Met His His Phe Ala Lys His Lys Ser Pro Leu260 265 270 Val Val Ile Leu Ile Ala Asp Met Phe Leu Leu Val Pro Pro Leu275 280 285 Met Asn Pro Ile Val Tyr Cys Val Lys Thr Arg Gln Ile Trp Glu290 295 300 Lys Ile Leu Gly Lys Leu Leu Asn Val Cys Gly Arg 305 310<210> SEQ ID NO 24 <211> LENGTH: 330 <212> TYPE: PRT <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7472089CD1 <400> SEQUENCE: 24 Met Ser Val LeuAsn Asn Thr Ile Ala Glu Pro Leu Ile Phe Leu 1 5 10 15 Leu Met Gly IlePro Gly Leu Lys Ala Thr Gln Tyr Trp Ile Ser 20 25 30 Ile Pro Phe Cys LeuLeu Tyr Val Val Ala Val Ser Gly Asn Ser 35 40 45 Met Ile Leu Phe Val ValLeu Cys Glu Arg Ser Leu His Lys Pro 50 55 60 Met Tyr Tyr Phe Leu Ser MetLeu Ser Ala Thr Asp Leu Ser Leu 65 70 75 Ser Leu Cys Thr Leu Ser Thr ThrLeu Gly Val Phe Trp Phe Glu 80 85 90 Ala Arg Glu Ile Asn Leu Asn Ala CysIle Ala Gln Met Phe Phe 95 100 105 Leu His Gly Phe Thr Phe Met Glu SerGly Val Leu Leu Ala Met 110 115 120 Ala Phe Asp Arg Phe Val Ala Ile CysTyr Pro Leu Arg Tyr Thr 125 130 135 Thr Ile Leu Thr Asn Ala Arg Ile AlaLys Ile Gly Met Ser Met 140 145 150 Leu Ile Arg Asn Val Ala Val Met LeuPro Val Met Leu Phe Val 155 160 165 Lys Arg Leu Ser Phe Cys Ser Ser MetVal Leu Ser His Ser Tyr 170 175 180 Cys Tyr His Val Asp Leu Ile Gln LeuSer Cys Thr Asp Asn Arg 185 190 195 Ile Asn Ser Ile Leu Gly Leu Phe AlaLeu Leu Ser Thr Thr Gly 200 205 210 Phe Asp Cys Pro Cys Ile Leu Leu SerTyr Ile Leu Ile Ile Arg 215 220 225 Ser Val Leu Ser Ile Ala Ser Ser GluGlu Arg Arg Lys Ala Phe 230 235 240 Asn Thr Cys Thr Ser His Ile Ser AlaVal Ser Ile Phe Tyr Leu 245 250 255 Pro Leu Ile Ser Leu Ser Leu Val HisArg Tyr Gly His Ser Ala 260 265 270 Pro Pro Phe Val His Ile Ile Met AlaAsn Val Phe Leu Leu Ile 275 280 285 Pro Pro Val Leu Asn Pro Ile Ile TyrSer Val Lys Ile Lys Gln 290 295 300 Ile Gln Lys Ala Ile Ile Lys Val LeuIle Gln Lys His Ser Lys 305 310 315 Ser Asn His Gln Leu Phe Leu Ile ArgAsp Lys Ala Ile Tyr Glu 320 325 330 <210> SEQ ID NO 25 <211> LENGTH: 314<212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7474902CD1<400> SEQUENCE: 25 Met Thr Leu Gly Ser Leu Gly Asn Ser Ser Ser Ser ValSer Ala 1 5 10 15 Thr Phe Leu Leu Ser Gly Ile Pro Gly Leu Glu Arg MetHis Ile 20 25 30 Trp Ile Ser Ile Pro Leu Cys Phe Met Tyr Leu Val Ser IlePro 35 40 45 Gly Asn Cys Thr Ile Leu Phe Ile Ile Lys Thr Glu Arg Ser Leu50 55 60 His Glu Pro Met Tyr Leu Phe Leu Ser Met Leu Ala Leu Ile Asp 6570 75 Leu Gly Leu Ser Leu Cys Thr Leu Pro Thr Val Leu Gly Ile Phe 80 8590 Trp Val Gly Ala Arg Glu Ile Ser His Asp Ala Cys Phe Ala Gln 95 100105 Leu Phe Phe Ile His Cys Phe Ser Phe Leu Glu Ser Ser Val Leu 110 115120 Leu Ser Met Ala Phe Asp Arg Phe Val Ala Ile Cys His Pro Leu 125 130135 His Tyr Val Ser Ile Leu Thr Asn Thr Val Ile Gly Arg Ile Gly 140 145150 Leu Val Ser Leu Gly Arg Ser Val Ala Leu Ile Phe Pro Leu Pro 155 160165 Phe Met Leu Lys Arg Phe Pro Tyr Cys Gly Ser Pro Val Leu Ser 170 175180 His Ser Tyr Cys Leu His Gln Glu Val Met Lys Leu Ala Cys Ala 185 190195 Asp Met Lys Ala Asn Ser Ile Tyr Gly Met Phe Val Ile Val Ser 200 205210 Thr Val Gly Ile Asp Ser Leu Leu Ile Leu Phe Ser Tyr Ala Leu 215 220225 Ile Leu Arg Thr Val Leu Ser Ile Ala Ser Arg Ala Glu Arg Phe 230 235240 Lys Ala Leu Asn Thr Cys Val Ser His Ile Cys Ala Val Leu Leu 245 250255 Phe Tyr Thr Pro Met Ile Gly Leu Ser Val Ile His Arg Phe Gly 260 265270 Lys Gln Ala Pro His Leu Val Gln Val Val Met Gly Phe Met Tyr 275 280285 Leu Leu Phe Pro Pro Val Met Asn Pro Ile Val Tyr Ser Val Lys 290 295300 Thr Lys Gln Ile Arg Asp Arg Val Thr His Ala Phe Cys Tyr 305 310<210> SEQ ID NO 26 <211> LENGTH: 320 <212> TYPE: PRT <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7475057CD1 <400> SEQUENCE: 26 Met Ala Glu ThrLeu Gln Leu Asn Ser Thr Phe Leu His Pro Asn 1 5 10 15 Phe Phe Ile LeuThr Gly Phe Pro Gly Leu Gly Ser Ala Gln Thr 20 25 30 Trp Leu Thr Leu ValPhe Gly Pro Ile Tyr Leu Leu Ala Leu Leu 35 40 45 Gly Asn Gly Ala Leu ProAla Val Val Trp Ile Asp Ser Thr Leu 50 55 60 His Gln Pro Met Phe Leu LeuLeu Ala Ile Leu Ala Ala Thr Asp 65 70 75 Leu Gly Leu Ala Thr Ser Ile AlaPro Gly Leu Leu Ala Val Leu 80 85 90 Trp Leu Gly Pro Arg Ser Val Pro TyrAla Val Cys Leu Val Gln 95 100 105 Met Phe Phe Val His Ala Leu Thr AlaMet Glu Ser Gly Val Leu 110 115 120 Leu Ala Met Ala Cys Asp Arg Ala AlaAla Ile Gly Arg Pro Leu 125 130 135 His Tyr Pro Val Leu Val Thr Lys AlaCys Val Gly Tyr Ala Ala 140 145 150 Leu Ala Leu Ala Leu Lys Ala Val AlaIle Val Val Pro Phe Pro 155 160 165 Leu Leu Val Ala Lys Phe Glu His PheGln Ala Lys Thr Ile Gly 170 175 180 His Thr Tyr Cys Ala His Met Ala ValVal Glu Leu Val Val Gly 185 190 195 Asn Thr Gln Ala Thr Asn Leu Tyr GlyLeu Ala Leu Ser Leu Ala 200 205 210 Ile Ser Gly Met Asp Ile Leu Gly IleThr Gly Ser Tyr Gly Leu 215 220 225 Ile Ala His Ala Val Leu Gln Leu ProThr Arg Glu Ala His Ala 230 235 240 Lys Ala Phe Gly Thr Cys Ser Ser HisIle Cys Val Ile Leu Ala 245 250 255 Phe Tyr Ile Pro Gly Leu Phe Ser TyrLeu Thr His Arg Phe Gly 260 265 270 His His Thr Val Pro Lys Pro Val HisIle Leu Leu Ser Asn Ile 275 280 285 Tyr Leu Leu Leu Pro Pro Ala Leu AsnPro Leu Ile Tyr Gly Ala 290 295 300 Arg Thr Lys Gln Ile Arg Asp Arg LeuLeu Glu Thr Phe Thr Phe 305 310 315 Arg Lys Ser Pro Leu 320 <210> SEQ IDNO 27 <211> LENGTH: 331 <212> TYPE: PRT <213> ORGANISM: Homo sapiens<220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION:Incyte ID No: 7475261CD1 <400> SEQUENCE: 27 Met Ser Gly Glu Asn Val ThrArg Val Gly Thr Phe Ile Leu Val 1 5 10 15 Gly Phe Pro Thr Ala Pro GlyLeu Gln Tyr Leu Leu Phe Leu Leu 20 25 30 Phe Leu Leu Thr Tyr Leu Phe ValLeu Val Glu Asn Leu Ala Ile 35 40 45 Ile Leu Thr Val Trp Ser Ser Thr SerLeu His Arg Pro Met Tyr 50 55 60 Tyr Phe Leu Ser Ser Met Ser Phe Leu GluIle Trp Tyr Val Ser 65 70 75 Asp Ile Thr Pro Lys Met Leu Glu Gly Phe LeuLeu Gln Gln Lys 80 85 90 Arg Ile Ser Phe Val Gly Cys Met Thr Gln Leu TyrPhe Phe Ser 95 100 105 Ser Leu Val Cys Thr Glu Cys Val Leu Leu Ala SerMet Ala Tyr 110 115 120 Asp Arg Tyr Val Ala Ile Cys His Pro Leu Arg TyrHis Val Leu 125 130 135 Val Thr Pro Gly Leu Cys Leu Gln Leu Val Gly PheSer Phe Val 140 145 150 Ser Gly Phe Thr Ile Ser Met Ile Lys Val Cys PheIle Ser Ser 155 160 165 Val Thr Phe Cys Gly Ser Asn Val Leu Asn His PhePhe Cys Asp 170 175 180 Ile Ser Pro Ile Leu Lys Leu Ala Cys Thr Asp PheSer Thr Ala 185 190 195 Glu Leu Val Asp Phe Ile Leu Ala Phe Ile Ile LeuVal Phe Pro 200 205 210 Leu Leu Ala Thr Met Leu Ser Tyr Ala His Ile ThrLeu Ala Val 215 220 225 Leu Arg Ile Pro Ser Ala Thr Gly Cys Trp Arg AlaPhe Phe Thr 230 235 240 Cys Ala Ser His Leu Thr Val Val Thr Val Phe TyrThr Ala Leu 245 250 255 Leu Phe Met Tyr Val Arg Pro Gln Ala Ile Asp SerArg Ser Ser 260 265 270 Asn Lys Leu Ile Ser Val Leu Tyr Thr Val Ile ThrPro Ile Leu 275 280 285 Asn Pro Leu Ile Tyr Cys Leu Arg Asn Lys Glu PheLys Asn Ala 290 295 300 Leu Lys Lys Ala Phe Gly Leu Thr Ser Cys Ala ValGlu Gly Arg 305 310 315 Leu Ser Ser Leu Leu Glu Leu His Leu Gln Ile HisSer Gln Pro 320 325 330 Leu <210> SEQ ID NO 28 <211> LENGTH: 311 <212>TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY:misc_feature <223> OTHER INFORMATION: Incyte ID No: 7475262CD1 <400>SEQUENCE: 28 Met Lys Gly Ala Asn Leu Ser Gln Gly Met Glu Phe Glu Leu Leu1 5 10 15 Gly Leu Thr Thr Asp Pro Gln Leu Gln Arg Leu Leu Phe Val Val 2025 30 Phe Leu Gly Met Tyr Thr Ala Thr Leu Leu Gly Asn Leu Val Met 35 4045 Phe Leu Leu Ile His Val Ser Ala Thr Leu His Thr Pro Met Tyr 50 55 60Ser Leu Leu Lys Ser Leu Ser Phe Leu Asp Phe Cys Tyr Ser Ser 65 70 75 ThrVal Val Pro Gln Thr Leu Val Asn Phe Leu Ala Lys Arg Lys 80 85 90 Val IleSer Tyr Phe Gly Cys Met Thr Gln Met Phe Phe Tyr Ala 95 100 105 Gly PheAla Thr Ser Glu Cys Tyr Leu Ile Ala Ala Met Ala Tyr 110 115 120 Asp ArgTyr Ala Ala Ile Cys Asn Pro Leu Leu Tyr Ser Thr Ile 125 130 135 Met SerPro Glu Val Cys Ala Ser Leu Ile Val Gly Ser Tyr Ser 140 145 150 Ala GlyPhe Leu Asn Ser Leu Ile His Thr Gly Cys Ile Phe Ser 155 160 165 Leu LysPhe Cys Gly Ala His Val Val Thr His Phe Phe Cys Asp 170 175 180 Gly ProPro Ile Leu Ser Leu Ser Cys Val Asp Thr Ser Leu Cys 185 190 195 Glu IleLeu Leu Phe Ile Phe Ala Gly Phe Asn Leu Leu Ser Cys 200 205 210 Thr LeuThr Ile Leu Ile Ser Tyr Phe Leu Ile Leu Asn Thr Ile 215 220 225 Leu LysMet Ser Ser Ala Gln Gly Arg Phe Lys Ala Phe Ser Thr 230 235 240 Cys AlaSer His Leu Thr Ala Ile Cys Leu Phe Phe Gly Thr Thr 245 250 255 Leu PheMet Tyr Leu Arg Pro Arg Ser Ser Tyr Ser Leu Thr Gln 260 265 270 Asp ArgThr Val Ala Val Ile Tyr Thr Val Val Ile Pro Val Leu 275 280 285 Asn ProLeu Met Tyr Ser Leu Arg Asn Lys Asp Val Lys Lys Ala 290 295 300 Leu IleLys Val Trp Gly Arg Lys Thr Met Glu 305 310 <210> SEQ ID NO 29 <211>LENGTH: 308 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE:<221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:7475266CD1 <400> SEQUENCE: 29 Met Thr Met Glu Asn Tyr Ser Met Ala AlaGln Phe Val Leu Asp 1 5 10 15 Gly Leu Thr Gln Gln Ala Glu Leu Gln LeuPro Leu Phe Leu Leu 20 25 30 Phe Leu Gly Ile Tyr Val Val Thr Val Val GlyAsn Leu Gly Met 35 40 45 Ile Leu Leu Ile Ala Val Ser Pro Leu Leu His ThrPro Met Tyr 50 55 60 Tyr Phe Leu Ser Ser Leu Ser Phe Val Asp Phe Cys TyrSer Ser 65 70 75 Val Ile Thr Pro Lys Met Leu Val Asn Phe Leu Gly Lys LysAsn 80 85 90 Thr Ile Leu Tyr Ser Glu Cys Met Val Gln Leu Val Phe Phe Val95 100 105 Val Phe Val Val Ala Glu Gly Tyr Leu Leu Thr Ala Met Ala Tyr110 115 120 Asp Arg Tyr Val Ala Ile Cys Ser Pro Leu Leu Tyr Asn Ala Ile125 130 135 Met Ser Ser Trp Val Cys Ser Leu Leu Val Leu Ala Ala Phe Phe140 145 150 Leu Gly Phe Leu Ser Ala Leu Thr His Thr Ser Ala Met Met Lys155 160 165 Leu Ser Phe Cys Lys Ser His Ile Ile Asn His Tyr Phe Cys Asp170 175 180 Val Leu Pro Leu Leu Asn Leu Ser Cys Ser Asn Thr His Leu Asn185 190 195 Glu Leu Leu Leu Phe Ile Ile Ala Gly Phe Asn Thr Leu Val Pro200 205 210 Thr Leu Ala Val Ala Val Ser Tyr Ala Phe Ile Leu Tyr Ser Ile215 220 225 Leu His Ile Arg Ser Ser Glu Gly Arg Ser Lys Ala Phe Gly Thr230 235 240 Cys Ser Ser His Leu Met Ala Val Val Ile Phe Phe Gly Ser Ile245 250 255 Thr Phe Met Tyr Phe Lys Pro Pro Ser Ser Asn Ser Leu Asp Gln260 265 270 Glu Lys Val Ser Ser Val Phe Tyr Thr Thr Val Ile Pro Met Leu275 280 285 Asn Pro Leu Ile Tyr Ser Leu Arg Asn Lys Asp Val Lys Lys Ala290 295 300 Leu Arg Lys Val Leu Val Gly Lys 305 <210> SEQ ID NO 30 <211>LENGTH: 298 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE:<221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:7475284CD1 <400> SEQUENCE: 30 Met Arg Asn His Thr Met Val Thr Glu PheIle Leu Leu Gly Ile 1 5 10 15 Pro Glu Thr Glu Gly Leu Glu Thr Ala LeuLeu Phe Leu Phe Ser 20 25 30 Ser Phe Tyr Leu Cys Thr Leu Leu Gly Asn ValLeu Ile Leu Thr 35 40 45 Ala Ile Ile Ser Ser Thr Arg Leu His Thr Pro MetTyr Phe Phe 50 55 60 Leu Gly Asn Leu Ser Ile Phe Asp Leu Gly Phe Ser SerThr Thr 65 70 75 Val Pro Lys Met Leu Phe Tyr Leu Ser Gly Asn Ser His AlaIle 80 85 90 Ser Tyr Ala Gly Cys Val Ser Gln Leu Phe Phe Tyr His Phe Leu95 100 105 Gly Cys Thr Glu Cys Phe Leu Tyr Thr Val Met Ala Cys Asp Arg110 115 120 Phe Val Ala Ile Cys Phe Pro Leu Arg Tyr Thr Val Ile Met Asn125 130 135 His Arg Val Cys Phe Met Leu Ala Thr Gly Thr Trp Met Ile Gly140 145 150 Cys Val His Ala Met Ile Leu Thr Pro Leu Thr Phe Gln Leu Pro155 160 165 Tyr Cys Gly Pro Asn Lys Val Gly Tyr Tyr Phe Cys Asp Ile Pro170 175 180 Ala Val Leu Pro Leu Ala Cys Lys Asp Thr Ser Leu Ala Gln Arg185 190 195 Val Gly Phe Thr Asn Val Gly Leu Leu Ser Leu Ile Cys Phe Phe200 205 210 Leu Ile Leu Val Ser Tyr Thr Cys Ile Gly Ile Ser Ile Ser Lys215 220 225 Ile Arg Ser Ala Glu Gly Arg Gln Arg Ala Phe Ser Thr Cys Ser230 235 240 Ala His Leu Thr Ala Ile Leu Cys Ala Tyr Gly Pro Val Ile Val245 250 255 Ile Tyr Leu Gln Pro Asn Pro Ser Ala Leu Leu Gly Ser Ile Ile260 265 270 Gln Ile Leu Asn Asn Leu Val Thr Pro Met Leu Asn Pro Leu Ile275 280 285 Tyr Ser Leu Arg Asn Lys Asp Val Lys Ser Asp Gln Pro 290 295<210> SEQ ID NO 31 <211> LENGTH: 317 <212> TYPE: PRT <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7475309CD1 <400> SEQUENCE: 31 Met Ser Gln ValThr Asn Thr Thr Gln Glu Gly Ile Tyr Phe Ile 1 5 10 15 Leu Thr Asp IlePro Gly Phe Glu Ala Ser His Ile Trp Ile Ser 20 25 30 Ile Pro Val Cys CysLeu Tyr Thr Ile Ser Ile Met Gly Asn Thr 35 40 45 Thr Ile Leu Thr Val IleArg Thr Glu Pro Ser Val His Gln Arg 50 55 60 Met Tyr Leu Phe Leu Ser MetLeu Ala Leu Thr Asp Leu Gly Leu 65 70 75 Thr Leu Thr Thr Leu Pro Thr ValMet Gln Leu Leu Trp Phe Asn 80 85 90 Val Arg Arg Ile Ser Ser Glu Ala CysPhe Ala Gln Phe Phe Phe 95 100 105 Leu His Gly Phe Ser Phe Met Glu SerSer Val Leu Leu Ala Met 110 115 120 Ser Val Asp Cys Tyr Val Ala Ile CysCys Pro Leu His Tyr Ala 125 130 135 Ser Ile Leu Thr Asn Glu Val Ile GlyArg Thr Gly Leu Ala Ile 140 145 150 Ile Cys Cys Cys Val Leu Ala Val LeuPro Ser Leu Phe Leu Leu 155 160 165 Lys Arg Leu Pro Phe Cys His Ser HisLeu Leu Ser Arg Ser Tyr 170 175 180 Cys Leu His Gln Asp Met Ile Arg LeuVal Cys Ala Asp Ile Arg 185 190 195 Leu Asn Ser Trp Tyr Gly Phe Ala LeuAla Leu Leu Ile Ile Ile 200 205 210 Val Asp Pro Leu Leu Ile Val Ile SerTyr Thr Leu Ile Leu Lys 215 220 225 Asn Ile Leu Gly Thr Ala Thr Trp AlaGlu Arg Leu Arg Ala Leu 230 235 240 Asn Asn Cys Leu Ser His Ile Leu AlaVal Leu Val Leu Tyr Ile 245 250 255 Pro Met Val Gly Val Ser Met Thr HisArg Phe Ala Lys His Ala 260 265 270 Ser Pro Leu Val His Val Ile Met AlaAsn Ile Tyr Leu Leu Ala 275 280 285 Pro Pro Val Met Asn Pro Ile Ile TyrSer Val Lys Asn Lys Gln 290 295 300 Ile Gln Trp Gly Met Leu Asn Phe LeuSer Leu Lys Asn Met His 305 310 315 Ser Arg <210> SEQ ID NO 32 <211>LENGTH: 309 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE:<221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:7477359CD1 <400> SEQUENCE: 32 Met Gly Leu Gly Asn Glu Ser Ser Leu MetAsp Phe Ile Leu Leu 1 5 10 15 Gly Phe Ser Asp His Pro Arg Leu Glu AlaVal Leu Phe Val Phe 20 25 30 Val Leu Phe Phe Tyr Leu Leu Thr Leu Val GlyAsn Phe Thr Ile 35 40 45 Ile Ile Ile Ser Tyr Leu Asp Pro Pro Leu His ThrPro Met Tyr 50 55 60 Phe Phe Leu Ser Asn Leu Ser Leu Leu Asp Ile Cys PheThr Thr 65 70 75 Ser Leu Ala Pro Gln Thr Leu Val Asn Leu Gln Arg Pro LysLys 80 85 90 Thr Ile Thr Tyr Gly Gly Cys Val Ala Gln Leu Tyr Ile Ser Leu95 100 105 Ala Leu Gly Ser Thr Glu Cys Ile Leu Leu Ala Asp Met Ala Leu110 115 120 Asp Arg Tyr Ile Ala Val Cys Lys Pro Leu His Tyr Val Val Ile125 130 135 Met Asn Pro Arg Leu Cys Gln Gln Leu Ala Ser Ile Ser Trp Leu140 145 150 Ser Gly Leu Ala Ser Ser Leu Ile His Ala Thr Phe Thr Leu Gln155 160 165 Leu Pro Leu Cys Gly Asn His Arg Leu Asp His Phe Ile Cys Glu170 175 180 Val Pro Ala Leu Leu Lys Leu Ala Cys Val Asp Thr Thr Val Asn185 190 195 Glu Leu Val Leu Phe Val Val Ser Val Leu Phe Val Val Ile Pro200 205 210 Pro Ala Leu Ile Ser Ile Ser Tyr Gly Phe Ile Thr Gln Ala Val215 220 225 Leu Arg Ile Lys Ser Val Glu Ala Arg His Lys Ala Phe Ser Thr230 235 240 Cys Ser Ser His Leu Thr Val Val Ile Ile Phe Tyr Gly Thr Ile245 250 255 Ile Tyr Val Tyr Leu Gln Pro Ser Asp Ser Tyr Ala Gln Asp Gln260 265 270 Gly Lys Phe Ile Ser Leu Phe Tyr Thr Met Val Thr Pro Thr Leu275 280 285 Asn Pro Ile Ile Tyr Thr Leu Arg Asn Lys Asp Met Lys Glu Ala290 295 300 Leu Arg Lys Leu Leu Ser Gly Lys Leu 305 <210> SEQ ID NO 33<211> LENGTH: 312 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 58004547CD1 <400> SEQUENCE: 33 Met Ser Gly Glu Asn Val Thr Lys ValSer Thr Phe Ile Leu Val 1 5 10 15 Gly Leu Pro Thr Ala Pro Gly Leu GlnTyr Leu Leu Phe Leu Leu 20 25 30 Phe Leu Leu Thr Tyr Leu Phe Val Leu ValGlu Asn Leu Ala Ile 35 40 45 Ile Leu Ile Val Trp Ser Ser Thr Ser Leu HisArg Pro Met Tyr 50 55 60 Tyr Phe Leu Ser Ser Met Ser Phe Leu Glu Ile TrpTyr Val Ser 65 70 75 Asp Ile Thr Pro Lys Met Leu Glu Gly Phe Leu Leu GlnGln Lys 80 85 90 Arg Ile Ser Phe Val Gly Cys Met Thr Gln Leu Tyr Phe PheSer 95 100 105 Ser Leu Val Cys Thr Glu Cys Val Leu Leu Ala Ser Met AlaTyr 110 115 120 Asp Arg Tyr Val Ala Ile Cys His Pro Leu Arg Tyr His ValLeu 125 130 135 Val Thr Pro Gly Leu Cys Leu Gln Leu Val Gly Phe Ser PheVal 140 145 150 Ser Gly Phe Thr Ile Ser Met Ile Lys Val Cys Phe Ile SerSer 155 160 165 Val Thr Phe Cys Gly Ser Asn Val Leu Asn His Phe Phe CysAsp 170 175 180 Ile Ser Pro Ile Leu Lys Leu Ala Cys Thr Asp Phe Ser ThrAla 185 190 195 Glu Leu Val Asp Phe Ile Leu Ala Phe Ile Ile Leu Val PhePro 200 205 210 Leu Leu Ala Thr Ile Leu Ser Tyr Trp His Ile Thr Leu AlaVal 215 220 225 Leu Arg Ile Pro Ser Ala Thr Gly Cys Trp Arg Ala Phe SerThr 230 235 240 Cys Ala Ser His Leu Thr Val Val Thr Val Phe Tyr Thr AlaLeu 245 250 255 Leu Phe Met Tyr Val Arg Pro Gln Ala Ile Asp Ser Gln SerSer 260 265 270 Asn Lys Leu Ile Ser Ala Val Tyr Thr Val Val Thr Pro IleIle 275 280 285 Asn Pro Leu Ile Tyr Cys Leu Arg Asn Lys Glu Phe Lys AspAla 290 295 300 Leu Lys Lys Ala Leu Gly Leu Gly Gln Thr Ser His 305 310<210> SEQ ID NO 34 <211> LENGTH: 310 <212> TYPE: PRT <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7476156CD1 <400> SEQUENCE: 34 Met Asp Lys GluAsn Ser Ser Met Val Thr Glu Phe Ile Phe Met 1 5 10 15 Gly Ile Thr GlnAsp Pro Gln Met Glu Ile Ile Phe Phe Val Val 20 25 30 Phe Leu Ile Val TyrLeu Val Asn Val Val Gly Asn Ile Gly Met 35 40 45 Ile Ile Leu Ile Thr ThrAsp Thr Gln Leu His Thr Pro Met Tyr 50 55 60 Phe Phe Leu Cys Asn Leu SerPhe Val Asp Leu Gly Tyr Ser Ser 65 70 75 Ala Ile Ala Pro Arg Met Leu AlaAsp Phe Leu Thr Asn His Lys 80 85 90 Val Ile Ser Phe Ser Ser Cys Ala ThrGln Phe Ala Phe Phe Val 95 100 105 Gly Phe Val Asp Ala Glu Cys Tyr ValLeu Ala Ala Met Ala Tyr 110 115 120 Gly Arg Phe Val Ala Ile Cys Arg ProLeu His Tyr Ser Thr Phe 125 130 135 Met Ser Lys Gln Val Cys Leu Ala LeuMet Leu Gly Ser Tyr Leu 140 145 150 Ala Gly Leu Val Ser Leu Val Ala HisThr Thr Leu Thr Phe Ser 155 160 165 Leu Ser Tyr Cys Gly Ser Asn Ile IleAsn His Phe Phe Cys Glu 170 175 180 Ile Pro Pro Leu Leu Ala Leu Ser CysSer Asp Thr Tyr Ile Ser 185 190 195 Glu Ile Leu Leu Phe Ser Leu Cys GlyPhe Ile Glu Phe Ser Thr 200 205 210 Ile Leu Ile Ile Phe Ile Ser Tyr ThrPhe Ile Leu Val Ala Ile 215 220 225 Ile Arg Met Arg Ser Ala Glu Gly ArgLeu Lys Ala Phe Ser Thr 230 235 240 Cys Gly Ser His Leu Thr Gly Ile ThrLeu Phe Tyr Gly Thr Val 245 250 255 Met Phe Met Tyr Leu Arg Pro Thr SerSer Tyr Ser Leu Asp Gln 260 265 270 Asp Lys Trp Ala Ser Val Phe Tyr ThrVal Ile Ile Pro Met Leu 275 280 285 Asn Pro Leu Ile Tyr Ser Leu Arg AsnLys Asp Val Lys Ala Ala 290 295 300 Phe Lys Lys Leu Ile Gly Lys Lys SerGln 305 310 <210> SEQ ID NO 35 <211> LENGTH: 314 <212> TYPE: PRT <213>ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 7475114CD1 <400> SEQUENCE: 35 Met AlaAsn Val Thr Leu Val Thr Gly Phe Leu Leu Met Gly Phe 1 5 10 15 Ser AsnIle Gln Lys Leu Arg Ile Leu Tyr Gly Val Leu Phe Leu 20 25 30 Leu Ile TyrLeu Ala Ala Leu Met Ser Asn Leu Leu Ile Ile Thr 35 40 45 Leu Ile Thr LeuAsp Val Lys Leu Gln Thr Pro Met Tyr Phe Phe 50 55 60 Leu Lys Asn Leu SerPhe Leu Asp Val Phe Leu Val Ser Val Pro 65 70 75 Ile Pro Lys Phe Ile ValAsn Asn Leu Thr His Asn Asn Ser Ile 80 85 90 Ser Ile Leu Gly Cys Ala PheGln Leu Leu Leu Met Thr Ser Phe 95 100 105 Ser Ala Gly Glu Ile Phe IleLeu Thr Ala Met Ser Tyr Asp Arg 110 115 120 Tyr Val Ala Ile Cys Cys ProLeu Asn Tyr Glu Val Ile Met Asn 125 130 135 Thr Gly Val Cys Val Leu MetAla Ser Val Ser Trp Ala Ile Gly 140 145 150 Gly Leu Phe Gly Thr Ala TyrThr Ala Gly Thr Phe Ser Met Pro 155 160 165 Phe Cys Gly Ser Ser Val IlePro Gln Phe Phe Cys Asp Val Pro 170 175 180 Ser Leu Leu Arg Ile Ser CysSer Glu Thr Leu Met Val Ile Tyr 185 190 195 Ala Gly Ile Gly Val Gly AlaCys Leu Ser Ile Ser Cys Phe Ile 200 205 210 Cys Ile Val Ile Ser Tyr IleTyr Ile Phe Ser Thr Val Leu Lys 215 220 225 Ile Pro Thr Thr Lys Gly GlnSer Lys Ala Phe Ser Thr Cys Phe 230 235 240 Pro His Leu Thr Val Phe ThrVal Phe Ile Ile Thr Ala Tyr Phe 245 250 255 Val Tyr Leu Lys Pro Pro SerAsn Ser Pro Ser Val Ile Asp Arg 260 265 270 Leu Leu Ser Val Ile Tyr ThrVal Met Pro Pro Val Phe Asn Pro 275 280 285 Val Thr Tyr Ser Leu Arg AsnAsn Asp Met Lys Cys Ala Leu Ile 290 295 300 Arg Leu Leu Gln Lys Thr TyrGly Gln Glu Ala Tyr Phe Ile 305 310 <210> SEQ ID NO 36 <211> LENGTH: 311<212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:55003505CD1 <400> SEQUENCE: 36 Met Ser Asn Ala Ser Leu Val Thr Ala PheIle Leu Thr Gly Leu 1 5 10 15 Pro His Ala Pro Gly Leu Asp Ala Leu LeuPhe Gly Ile Phe Leu 20 25 30 Val Val Tyr Val Leu Thr Val Leu Gly Asn LeuLeu Ile Leu Leu 35 40 45 Val Ile Arg Val Asp Ser His Leu His Thr Pro MetTyr Tyr Phe 50 55 60 Leu Thr Asn Leu Ser Phe Ile Asp Met Trp Phe Ser ThrVal Thr 65 70 75 Val Pro Lys Met Leu Met Thr Leu Val Ser Pro Ser Gly ArgAla 80 85 90 Ile Ser Phe His Ser Cys Val Ala Gln Leu Tyr Phe Phe His Phe95 100 105 Leu Gly Ser Thr Glu Cys Phe Leu Tyr Thr Val Met Ser Tyr Asp110 115 120 Arg Tyr Leu Ala Ile Ser Tyr Pro Leu Arg Tyr Thr Ser Met Met125 130 135 Ser Gly Ser Arg Cys Ala Leu Leu Ala Thr Gly Thr Trp Leu Ser140 145 150 Gly Ser Leu His Ser Ala Val Gln Thr Ile Leu Thr Phe His Leu155 160 165 Pro Tyr Cys Gly Pro Asn Gln Ile Gln His Tyr Phe Cys Asp Ala170 175 180 Pro Pro Ile Leu Lys Leu Ala Cys Ala Asp Thr Ser Ala Asn Val185 190 195 Met Val Ile Phe Val Asp Ile Gly Ile Val Ala Ser Gly Cys Phe200 205 210 Val Leu Ile Val Leu Ser Tyr Val Ser Ile Val Cys Ser Ile Leu215 220 225 Arg Ile Arg Thr Ser Asp Gly Arg Arg Arg Ala Phe Gln Thr Cys230 235 240 Ala Ser His Cys Ile Val Val Leu Cys Phe Phe Val Pro Cys Val245 250 255 Val Ile Tyr Leu Arg Pro Gly Ser Met Asp Ala Met Asp Gly Val260 265 270 Val Ala Ile Phe Tyr Thr Val Leu Thr Pro Leu Leu Asn Pro Val275 280 285 Val Tyr Thr Leu Arg Asn Lys Glu Val Lys Lys Ala Val Leu Lys290 295 300 Leu Arg Asp Lys Val Ala His Pro Gln Arg Lys 305 310 <210>SEQ ID NO 37 <211> LENGTH: 337 <212> TYPE: PRT <213> ORGANISM: Homosapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7474916CD1 <400> SEQUENCE: 37 Met Glu Gly LysAsn Gln Thr Asn Ile Ser Glu Phe Leu Leu Leu 1 5 10 15 Gly Phe Ser SerTrp Gln Gln Gln Gln Val Leu Leu Phe Ala Leu 20 25 30 Phe Leu Cys Leu TyrLeu Thr Gly Leu Phe Gly Asn Leu Leu Ile 35 40 45 Leu Leu Ala Ile Gly SerAsp His Cys Leu His Thr Pro Met Tyr 50 55 60 Phe Phe Leu Ala Asn Leu SerLeu Val Asp Leu Cys Leu Pro Ser 65 70 75 Ala Thr Val Pro Lys Met Leu LeuAsn Ile Gln Thr Gln Thr Gln 80 85 90 Thr Ile Ser Tyr Pro Gly Cys Leu AlaGln Met Tyr Phe Cys Met 95 100 105 Met Phe Ala Asn Met Asp Asn Phe LeuLeu Thr Val Met Ala Tyr 110 115 120 Asp Arg Tyr Val Ala Ile Cys His ProLeu His Tyr Ser Thr Ile 125 130 135 Met Ala Leu Arg Leu Cys Ala Ser LeuVal Ala Ala Pro Trp Val 140 145 150 Ile Ala Ile Leu Asn Pro Leu Leu HisThr Leu Met Met Ala His 155 160 165 Leu His Phe Cys Ser Asp Asn Val IleHis His Phe Phe Cys Asp 170 175 180 Ile Asn Ser Leu Leu Pro Leu Ser CysSer Asp Thr Ser Leu Asn 185 190 195 Gln Leu Ser Val Leu Ala Thr Val GlyLeu Ile Phe Val Val Pro 200 205 210 Ser Val Cys Ile Leu Val Ser Tyr IleLeu Ile Val Ser Ala Val 215 220 225 Met Lys Val Pro Ser Ala Gln Gly LysLeu Lys Ala Phe Ser Thr 230 235 240 Cys Gly Ser His Leu Ala Leu Val IleLeu Phe Tyr Gly Ala Asn 245 250 255 Thr Gly Val Tyr Met Ser Pro Leu SerAsn His Ser Thr Glu Lys 260 265 270 Asp Ser Ala Ala Ser Val Ile Phe MetVal Val Ala Pro Val Leu 275 280 285 Asn Pro Phe Ile Tyr Ser Leu Arg AsnAsn Glu Leu Lys Gly Thr 290 295 300 Leu Lys Lys Thr Leu Ser Arg Pro GlyAla Val Ala His Ala Cys 305 310 315 Asn Pro Ser Thr Leu Gly Gly Arg GlyGly Trp Ile Met Arg Ser 320 325 330 Gly Asp Arg Asp His Pro Gly 335<210> SEQ ID NO 38 <211> LENGTH: 325 <212> TYPE: PRT <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7472365CD1 <400> SEQUENCE: 38 Met Phe Leu ProAsn Asp Thr Gln Phe His Pro Ser Ser Phe Leu 1 5 10 15 Leu Leu Gly IlePro Gly Leu Glu Thr Leu His Ile Trp Ile Gly 20 25 30 Phe Pro Phe Cys AlaVal Tyr Met Ile Ala Leu Ile Gly Asn Phe 35 40 45 Thr Ile Leu Leu Val IleLys Thr Asp Ser Ser Leu His Gln Pro 50 55 60 Met Phe Tyr Phe Leu Ala MetLeu Ala Thr Thr Asp Val Gly Leu 65 70 75 Ser Thr Ala Thr Ile Pro Lys MetLeu Gly Ile Phe Trp Ile Asn 80 85 90 Leu Arg Gly Ile Ile Phe Glu Ala CysLeu Thr Gln Met Phe Phe 95 100 105 Ile His Asn Phe Thr Leu Met Glu SerAla Val Leu Val Ala Met 110 115 120 Ala Tyr Asp Ser Tyr Val Ala Ile CysAsn Pro Leu Gln Tyr Ser 125 130 135 Ala Ile Leu Thr Asn Lys Val Val SerVal Ile Gly Leu Gly Val 140 145 150 Phe Val Arg Ala Leu Ile Phe Val IlePro Ser Ile Leu Leu Ile 155 160 165 Leu Arg Leu Pro Phe Cys Gly Asn HisVal Ile Pro His Thr Tyr 170 175 180 Cys Glu His Met Gly Leu Ala His LeuSer Cys Ala Ser Ile Lys 185 190 195 Ile Asn Ile Ile Tyr Gly Leu Cys AlaIle Cys Asn Leu Val Phe 200 205 210 Asp Ile Thr Val Ile Ala Leu Ser TyrVal His Ile Leu Cys Ala 215 220 225 Val Phe Arg Leu Pro Thr His Glu ProArg Leu Lys Ser Leu Ser 230 235 240 Thr Cys Gly Ser His Val Cys Val IleLeu Ala Phe Tyr Thr Pro 245 250 255 Ala Leu Phe Ser Phe Met Thr His CysPhe Gly Arg Asn Val Pro 260 265 270 Arg Tyr Ile His Ile Leu Leu Ala AsnLeu Tyr Val Val Val Pro 275 280 285 Pro Met Leu Asn Pro Val Ile Tyr GlyVal Arg Thr Lys Gln Ile 290 295 300 Tyr Lys Cys Val Lys Lys Ile Leu LeuGln Glu Gln Gly Met Glu 305 310 315 Lys Glu Glu Tyr Leu Ile His Thr ArgPhe 320 325 <210> SEQ ID NO 39 <211> LENGTH: 327 <212> TYPE: PRT <213>ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 7475230CD1 <400> SEQUENCE: 39 Met LeuHis Thr Asn Asn Thr Gln Phe His Pro Ser Thr Phe Leu 1 5 10 15 Val ValGly Val Pro Gly Leu Glu Asp Val His Val Trp Ile Gly 20 25 30 Phe Pro PhePhe Ala Val Tyr Leu Thr Ala Leu Leu Gly Asn Ile 35 40 45 Ile Ile Leu PheVal Ile Gln Thr Glu Gln Ser Leu His Gln Pro 50 55 60 Met Phe Tyr Phe LeuAla Met Leu Ala Gly Thr Asp Leu Gly Leu 65 70 75 Ser Thr Ala Thr Ile ProLys Met Leu Gly Ile Phe Trp Phe Asn 80 85 90 Leu Gly Glu Ile Ala Phe GlyAla Cys Ile Thr Gln Met Tyr Thr 95 100 105 Ile His Ile Cys Thr Gly LeuGlu Ser Val Val Leu Thr Val Thr 110 115 120 Gly Ile Asp Arg Tyr Ile AlaIle Cys Asn Pro Leu Arg Tyr Ser 125 130 135 Met Ile Leu Thr Asn Lys ValIle Ala Ile Leu Gly Ile Val Ile 140 145 150 Ile Val Arg Thr Leu Val PheVal Thr Pro Phe Thr Phe Leu Thr 155 160 165 Leu Arg Leu Pro Phe Cys GlyVal Arg Ile Ile Pro His Thr Tyr 170 175 180 Cys Glu His Met Gly Leu AlaLys Leu Ala Cys Ala Ser Ile Asn 185 190 195 Val Ile Tyr Gly Leu Ile AlaPhe Ser Val Gly Tyr Ile Asp Ile 200 205 210 Ser Val Ile Gly Phe Ser TyrVal Gln Ile Leu Arg Ala Val Phe 215 220 225 His Leu Pro Ala Trp Asp AlaArg Leu Lys Ala Leu Ser Thr Cys 230 235 240 Gly Ser His Val Cys Val MetLeu Ala Phe Tyr Leu Pro Ala Leu 245 250 255 Phe Ser Phe Met Thr His ArgPhe Gly His Asn Ile Pro His Tyr 260 265 270 Ile His Ile Leu Leu Ala AsnLeu Tyr Val Val Phe Pro Pro Ala 275 280 285 Leu Asn Ser Val Ile Tyr GlyVal Lys Thr Lys Gln Ile Arg Glu 290 295 300 Gln Val Leu Arg Ile Leu AsnPro Lys Ser Phe Trp His Phe Asp 305 310 315 Pro Lys Arg Ile Phe His AsnAsn Ser Val Arg Gln 320 325 <210> SEQ ID NO 40 <211> LENGTH: 313 <212>TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY:misc_feature <223> OTHER INFORMATION: Incyte ID No: 7475229CD1 <400>SEQUENCE: 40 Met Pro Ile Ala Asn Asp Thr Gln Phe His Thr Ser Ser Phe Leu1 5 10 15 Leu Leu Gly Ile Pro Gly Leu Glu Asp Val His Ile Trp Ile Gly 2025 30 Phe Pro Phe Phe Ser Val Tyr Leu Ile Ala Leu Leu Gly Asn Ala 35 4045 Ala Ile Phe Phe Val Ile Gln Thr Glu Gln Ser Leu His Glu Pro 50 55 60Met Tyr Tyr Cys Leu Ala Met Leu Asp Ser Ile Asp Leu Ser Leu 65 70 75 SerThr Ala Thr Ile Pro Lys Met Leu Gly Ile Phe Trp Phe Asn 80 85 90 Ile LysGlu Ile Ser Phe Gly Gly Tyr Leu Ser Gln Met Phe Phe 95 100 105 Ile HisPhe Phe Thr Val Met Glu Ser Ile Val Leu Val Ala Met 110 115 120 Ala PheAsp Arg Tyr Ile Ala Ile Cys Lys Pro Leu Trp Tyr Thr 125 130 135 Met IleLeu Thr Ser Lys Ile Ile Ser Leu Ile Ala Gly Ile Ala 140 145 150 Val LeuArg Ser Leu Tyr Met Val Ile Pro Leu Val Phe Leu Leu 155 160 165 Leu ArgLeu Pro Phe Cys Gly His Arg Ile Ile Pro His Thr Tyr 170 175 180 Cys GluHis Met Gly Ile Ala Arg Leu Ala Cys Ala Ser Ile Lys 185 190 195 Val AsnIle Met Phe Gly Leu Gly Ser Ile Ser Leu Leu Leu Leu 200 205 210 Asp ValLeu Leu Ile Ile Leu Ser His Ile Arg Ile Leu Tyr Ala 215 220 225 Val PheCys Leu Pro Ser Trp Glu Ala Arg Leu Lys Ala Leu Asn 230 235 240 Thr CysGly Ser His Ile Gly Val Ile Leu Ala Phe Ser Thr Pro 245 250 255 Ala PhePhe Ser Phe Phe Thr His Cys Phe Gly His Asp Ile Pro 260 265 270 Gln TyrIle His Ile Phe Leu Ala Asn Leu Tyr Val Val Val Pro 275 280 285 Pro ThrLeu Asn Pro Val Ile Tyr Gly Val Arg Thr Lys His Ile 290 295 300 Arg GluThr Val Leu Arg Ile Phe Phe Lys Thr Asp His 305 310 <210> SEQ ID NO 41<211> LENGTH: 311 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 7477367CD1 <400> SEQUENCE: 41 Met Ala His Thr Asn Glu Ser Met ValSer Glu Phe Val Leu Leu 1 5 10 15 Gly Leu Ser Asn Ser Trp Gly Leu GlnLeu Phe Phe Phe Ala Ile 20 25 30 Phe Ser Ile Val Tyr Val Thr Ser Val LeuGly Asn Val Leu Ile 35 40 45 Ile Val Ile Ile Ser Phe Asp Ser His Leu AsnSer Pro Met Tyr 50 55 60 Phe Leu Leu Ser Asn Leu Ser Phe Ile Asp Ile CysGln Ser Asn 65 70 75 Phe Ala Thr Pro Lys Met Leu Val Asp Phe Phe Ile GluArg Lys 80 85 90 Thr Ile Ser Phe Glu Gly Cys Met Ala Gln Ile Phe Val LeuHis 95 100 105 Ser Phe Val Gly Ser Glu Met Met Leu Leu Val Ala Met AlaTyr 110 115 120 Asp Arg Phe Ile Ala Ile Cys Lys Pro Leu His Tyr Ser ThrIle 125 130 135 Met Asn Arg Arg Leu Cys Val Ile Phe Val Ser Ile Ser TrpAla 140 145 150 Val Gly Val Leu His Ser Val Ser His Leu Ala Phe Thr ValAsp 155 160 165 Leu Pro Phe Cys Gly Pro Asn Glu Val Asp Ser Phe Phe CysAsp 170 175 180 Leu Pro Leu Val Ile Glu Leu Ala Cys Met Asp Thr Tyr GluMet 185 190 195 Glu Ile Met Thr Leu Thr Asn Ser Gly Leu Ile Ser Leu SerCys 200 205 210 Phe Leu Ala Leu Ile Ile Ser Tyr Thr Ile Ile Leu Ile GlyVal 215 220 225 Arg Cys Arg Ser Ser Ser Gly Ser Ser Lys Ala Leu Ser ThrLeu 230 235 240 Thr Ala His Ile Thr Val Val Ile Leu Phe Phe Gly Pro CysIle 245 250 255 Tyr Phe Tyr Ile Trp Pro Phe Ser Arg Leu Pro Val Asp LysPhe 260 265 270 Leu Ser Val Phe Tyr Thr Val Cys Thr Pro Leu Leu Asn ProIle 275 280 285 Ile Tyr Ser Leu Arg Asn Glu Asp Val Lys Ala Ala Met TrpLys 290 295 300 Leu Arg Asn His His Val Asn Ser Trp Lys Asn 305 310<210> SEQ ID NO 42 <211> LENGTH: 304 <212> TYPE: PRT <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7477936CD1 <400> SEQUENCE: 42 Met Glu Arg AlaAsn His Ser Val Val Ser Glu Phe Ile Leu Leu 1 5 10 15 Gly Leu Ser LysSer Gln Asn Leu Gln Ile Leu Phe Phe Leu Gly 20 25 30 Phe Ser Val Val PheVal Gly Ile Val Leu Gly Asn Leu Leu Ile 35 40 45 Leu Val Thr Val Thr PheAsp Ser Leu Leu His Thr Pro Met Tyr 50 55 60 Phe Leu Leu Ser Asn Leu SerCys Ile Asp Met Ile Leu Ala Ser 65 70 75 Phe Ala Thr Pro Lys Met Ile ValAsp Phe Leu Arg Glu Arg Lys 80 85 90 Thr Ile Ser Trp Trp Gly Cys Tyr SerGln Met Phe Phe Met His 95 100 105 Leu Leu Gly Gly Ser Glu Met Met LeuLeu Val Ala Met Ala Ile 110 115 120 Asp Arg Tyr Val Ala Ile Cys Lys ProLeu His Tyr Met Thr Ile 125 130 135 Met Ser Pro Arg Val Leu Thr Gly LeuLeu Leu Ser Ser Tyr Ala 140 145 150 Val Gly Phe Val His Ser Ser Ser GlnMet Ala Phe Met Leu Thr 155 160 165 Leu Pro Phe Cys Gly Pro Asn Val IleAsp Ser Phe Phe Cys Asp 170 175 180 Leu Pro Leu Val Ile Lys Leu Ala CysLys Asp Thr Tyr Ile Leu 185 190 195 Gln Leu Leu Val Ile Ala Asp Ser GlyLeu Leu Ser Leu Val Cys 200 205 210 Phe Leu Leu Leu Leu Val Ser Tyr GlyVal Ile Ile Phe Ser Val 215 220 225 Arg Tyr Arg Ala Ala Ser Arg Ser SerLys Ala Phe Ser Thr Leu 230 235 240 Ser Ala His Ile Thr Val Val Thr LeuPhe Phe Ala Pro Cys Val 245 250 255 Phe Ile Tyr Val Trp Pro Phe Ser ArgTyr Ser Val Asp Lys Ile 260 265 270 Leu Ser Val Phe Tyr Thr Ile Phe ThrPro Leu Leu Asn Pro Ile 275 280 285 Ile Tyr Thr Leu Arg Asn Gln Glu ValLys Ala Ala Ile Lys Lys 290 295 300 Arg Leu Cys Ile <210> SEQ ID NO 43<211> LENGTH: 311 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 7475214CD1 <400> SEQUENCE: 43 Met Glu Lys Ile Asn Asn Val Thr GluPhe Ile Phe Trp Gly Leu 1 5 10 15 Ser Gln Ser Pro Glu Ile Glu Lys ValCys Phe Val Val Phe Ser 20 25 30 Phe Phe Tyr Ile Ile Ile Leu Leu Gly AsnLeu Leu Ile Met Leu 35 40 45 Thr Val Cys Leu Ser Asn Leu Phe Lys Ser ProMet Tyr Phe Phe 50 55 60 Leu Ser Phe Leu Ser Phe Val Asp Ile Cys Tyr SerSer Val Thr 65 70 75 Ala Pro Lys Met Ile Val Asp Leu Leu Ala Lys Asp LysThr Ile 80 85 90 Ser Tyr Val Gly Cys Met Leu Gln Leu Leu Gly Val His PhePhe 95 100 105 Gly Cys Thr Glu Ile Phe Ile Leu Thr Val Met Ala Tyr AspArg 110 115 120 Tyr Val Ala Ile Cys Lys Pro Leu His Tyr Met Thr Ile MetAsn 125 130 135 Arg Glu Thr Cys Asn Lys Met Leu Leu Gly Thr Trp Val GlyGly 140 145 150 Phe Leu His Ser Ile Ile Gln Val Ala Leu Val Val Gln LeuPro 155 160 165 Phe Cys Gly Pro Asn Glu Ile Asp His Tyr Phe Cys Asp ValHis 170 175 180 Pro Val Leu Lys Leu Ala Cys Thr Glu Thr Tyr Ile Val GlyVal 185 190 195 Val Val Thr Ala Asn Ser Gly Thr Ile Ala Leu Gly Ser PheVal 200 205 210 Ile Leu Leu Ile Ser Tyr Ser Ile Ile Leu Val Ser Leu ArgLys 215 220 225 Gln Ser Ala Glu Gly Arg Arg Lys Ala Leu Ser Thr Cys GlySer 230 235 240 His Ile Ala Met Val Val Ile Phe Phe Gly Pro Cys Thr PheMet 245 250 255 Tyr Met Arg Pro Asp Thr Thr Phe Ser Glu Asp Lys Met ValAla 260 265 270 Val Phe Tyr Thr Ile Ile Thr Pro Met Leu Asn Pro Leu IleTyr 275 280 285 Thr Leu Arg Asn Ala Glu Val Lys Asn Ala Met Lys Lys LeuTrp 290 295 300 Gly Arg Asn Val Phe Leu Glu Ala Lys Gly Lys 305 310<210> SEQ ID NO 44 <211> LENGTH: 311 <212> TYPE: PRT <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 55036157CD1 <400> SEQUENCE: 44 Met Ala AlaGlu Asn His Ser Phe Val Thr Lys Phe Ile Leu Val 1 5 10 15 Gly Leu ThrGlu Lys Ser Glu Leu Gln Leu Pro Leu Phe Leu Val 20 25 30 Phe Leu Gly IleTyr Val Val Thr Val Leu Gly Asn Leu Gly Met 35 40 45 Ile Thr Leu Ile GlyLeu Ser Ser His Leu His Thr Pro Met Tyr 50 55 60 Cys Phe Leu Ser Ser LeuSer Phe Ile Asp Phe Cys His Ser Thr 65 70 75 Val Ile Thr Pro Lys Met LeuVal Asn Phe Val Thr Glu Lys Asn 80 85 90 Ile Ile Ser Tyr Pro Glu Cys MetThr Gln Leu Tyr Phe Phe Leu 95 100 105 Val Phe Ala Ile Ala Glu Cys HisMet Leu Ala Ala Met Ala Tyr 110 115 120 Asp Gly Tyr Val Ala Ile Cys SerPro Leu Leu Tyr Ser Ile Ile 125 130 135 Ile Ser Asn Lys Ala Cys Phe SerLeu Ile Leu Val Val Tyr Val 140 145 150 Ile Gly Leu Ile Cys Ala Ser AlaHis Ile Gly Cys Met Phe Arg 155 160 165 Val Gln Phe Cys Lys Phe Asp ValIle Asn His Tyr Phe Cys Asp 170 175 180 Leu Ile Ser Ile Leu Lys Leu SerCys Ser Ser Thr Tyr Ile Asn 185 190 195 Glu Leu Leu Ile Leu Ile Phe SerGly Ile Asn Ile Leu Val Pro 200 205 210 Ser Leu Thr Ile Leu Ser Ser TyrIle Phe Ile Ile Ala Ser Ile 215 220 225 Leu Arg Ile Arg Tyr Thr Glu GlyArg Ser Lys Ala Phe Ser Thr 230 235 240 Cys Ser Ser His Ile Ser Ala ValSer Val Phe Phe Gly Ser Ala 245 250 255 Ala Phe Met Tyr Leu Gln Pro SerSer Val Ser Ser Met Asp Gln 260 265 270 Gly Lys Val Ser Ser Val Phe TyrThr Ile Val Val Pro Met Leu 275 280 285 Asn Pro Leu Ile Tyr Ser Leu ArgAsn Lys Asp Val His Val Ala 290 295 300 Leu Lys Lys Thr Leu Gly Lys ArgThr Phe Leu 305 310 <210> SEQ ID NO 45 <211> LENGTH: 329 <212> TYPE: PRT<213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature<223> OTHER INFORMATION: Incyte ID No: 7475226CD1 <400> SEQUENCE: 45 MetThr Leu Val Ser Phe Phe Ser Phe Leu Ser Lys Pro Leu Ile 1 5 10 15 MetLeu Leu Ser Asn Ser Ser Trp Arg Leu Ser Gln Pro Ser Phe 20 25 30 Leu LeuVal Gly Ile Pro Gly Leu Glu Glu Ser Gln His Trp Ile 35 40 45 Ala Leu ProLeu Gly Ile Leu Tyr Leu Leu Ala Leu Val Gly Asn 50 55 60 Val Thr Ile LeuPhe Ile Ile Trp Met Asp Pro Ser Leu His Gln 65 70 75 Ser Met Tyr Leu PheLeu Ser Met Leu Ala Ala Ile Asp Leu Val 80 85 90 Leu Ala Ser Ser Thr AlaPro Lys Ala Leu Ala Val Leu Leu Val 95 100 105 His Ala His Glu Ile GlyTyr Ile Val Cys Leu Ile Gln Met Phe 110 115 120 Phe Ile His Ala Phe SerSer Met Glu Ser Gly Val Leu Val Ala 125 130 135 Met Ala Leu Asp Arg TyrVal Ala Ile Cys His Pro Leu His His 140 145 150 Ser Thr Ile Leu His ProGly Val Ile Gly Arg Ile Gly Met Val 155 160 165 Val Leu Val Arg Gly LeuLeu Leu Leu Ile Pro Phe Pro Ile Leu 170 175 180 Leu Gly Thr Leu Ile PheCys Gln Ala Thr Ile Ile Gly His Ala 185 190 195 Tyr Cys Glu His Met AlaVal Val Lys Leu Ala Cys Ser Glu Thr 200 205 210 Thr Val Asn Arg Ala TyrGly Leu Thr Met Ala Leu Leu Val Ile 215 220 225 Gly Leu Asp Val Leu AlaIle Gly Val Ser Tyr Ala His Ile Leu 230 235 240 Gln Ala Val Leu Lys ValPro Gly Ser Glu Ala Arg Leu Lys Ala 245 250 255 Phe Ser Thr Cys Gly SerHis Ile Cys Val Ile Leu Val Phe Tyr 260 265 270 Val Pro Gly Ile Phe SerPhe Leu Thr His Arg Phe Gly His His 275 280 285 Val Pro His His Val HisVal Leu Leu Ala Thr Arg Tyr Leu Leu 290 295 300 Met Pro Pro Ala Leu AsnPro Leu Val Tyr Gly Val Lys Thr Gln 305 310 315 Gln Ile Arg Gln Arg ValLeu Arg Val Phe Thr Gln Lys Asp 320 325 <210> SEQ ID NO 46 <211> LENGTH:312 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7477353CD1<400> SEQUENCE: 46 Met Glu Asn Tyr Asn Gln Thr Ser Thr Asp Phe Ile LeuLeu Gly 1 5 10 15 Leu Phe Pro Pro Ser Lys Ile Gly Leu Phe Leu Phe IleLeu Phe 20 25 30 Val Leu Ile Phe Leu Met Ala Leu Ile Gly Asn Leu Ser MetIle 35 40 45 Leu Leu Ile Phe Leu Asp Thr His Leu His Thr Pro Met Tyr Phe50 55 60 Leu Leu Ser Gln Leu Ser Leu Ile Asp Leu Asn Tyr Ile Ser Thr 6570 75 Ile Val Pro Lys Met Ala Ser Asp Phe Leu Tyr Gly Asn Lys Ser 80 8590 Ile Ser Phe Ile Gly Cys Gly Ile Gln Ser Phe Phe Phe Met Thr 95 100105 Phe Ala Gly Ala Glu Ala Leu Leu Leu Thr Ser Met Ala Tyr Asp 110 115120 Arg Tyr Val Ala Ile Cys Phe Pro Leu His Tyr Pro Ile Arg Met 125 130135 Ser Lys Arg Met Tyr Val Leu Met Ile Thr Gly Ser Trp Met Ile 140 145150 Gly Ser Ile Asn Ser Cys Ala His Thr Val Tyr Ala Phe Arg Ile 155 160165 Pro Tyr Cys Lys Ser Arg Ala Ile Asn His Phe Phe Cys Asp Val 170 175180 Pro Ala Met Leu Thr Leu Ala Cys Thr Asp Thr Trp Val Tyr Glu 185 190195 Tyr Thr Val Phe Leu Ser Ser Thr Ile Phe Leu Val Phe Pro Phe 200 205210 Thr Gly Ile Ala Cys Ser Tyr Gly Trp Val Leu Leu Ala Val Tyr 215 220225 Arg Met His Ser Ala Glu Gly Arg Lys Lys Ala Tyr Ser Thr Cys 230 235240 Ser Thr His Leu Thr Val Val Thr Phe Tyr Tyr Ala Pro Phe Ala 245 250255 Tyr Thr Tyr Leu Cys Pro Arg Ser Leu Arg Ser Leu Thr Glu Asp 260 265270 Lys Val Leu Ala Val Phe Tyr Thr Ile Leu Thr Pro Met Leu Asn 275 280285 Pro Ile Ile Tyr Ser Leu Arg Asn Lys Glu Val Met Gly Ala Leu 290 295300 Thr Arg Val Ile Gln Asn Ile Phe Ser Val Lys Met 305 310 <210> SEQ IDNO 47 <211> LENGTH: 347 <212> TYPE: PRT <213> ORGANISM: Homo sapiens<220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION:Incyte ID No: 55036208CD1 <400> SEQUENCE: 47 Met Ala Trp Glu Asn Gln ThrPhe Asn Ser Asp Phe Ile Leu Leu 1 5 10 15 Gly Ile Phe Asn His Ser ProPro His Thr Phe Leu Phe Phe Leu 20 25 30 Val Leu Gly Ile Phe Leu Val AlaPhe Met Gly Asn Ser Val Met 35 40 45 Val Leu Leu Ile Tyr Leu Asp Thr GlnLeu His Thr Pro Met Tyr 50 55 60 Phe Leu Leu Ser Gln Leu Ser Leu Met AspLeu Met Leu Ile Cys 65 70 75 Thr Thr Val Pro Lys Met Ala Phe Asn Tyr LeuSer Gly Ser Lys 80 85 90 Ser Ile Ser Met Ala Gly Cys Val Thr Gln Ile PhePhe Tyr Ile 95 100 105 Ser Leu Ser Gly Ser Glu Cys Phe Leu Leu Ala ValMet Ala Tyr 110 115 120 Asp Arg Tyr Ile Ala Ile Cys His Pro Leu Arg TyrThr Asn Leu 125 130 135 Met Asn Pro Lys Ile Cys Gly Leu Met Ala Thr PheSer Trp Ile 140 145 150 Leu Gly Ser Thr Asp Gly Ile Ile Asp Ala Val AlaThr Phe Ser 155 160 165 Phe Ser Phe Cys Gly Ser Arg Glu Ile Ala His PhePhe Cys Glu 170 175 180 Phe Pro Ser Leu Leu Ile Leu Ser Cys Asn Asp ThrSer Ile Phe 185 190 195 Glu Glu Val Ile Phe Ile Cys Cys Ile Val Met LeuVal Phe Pro 200 205 210 Val Ala Ile Ile Ile Ala Ser Tyr Ala Gly Val IleLeu Ala Val 215 220 225 Ile His Met Gly Ser Gly Glu Gly Arg Arg Lys ThrPhe Thr Thr 230 235 240 Cys Ser Ser His Leu Met Val Val Gly Met Tyr TyrGly Ala Ala 245 250 255 Leu Phe Met Tyr Ile Arg Pro Thr Ser Asp His SerPro Thr Gln 260 265 270 Asp Lys Met Val Ser Val Phe Tyr Thr Ile Leu ThrPro Met Leu 275 280 285 Asn Pro Leu Ile Tyr Ser Leu Arg Asn Lys Glu ValThr Arg Ala 290 295 300 Phe Met Lys Ile Leu Gly Lys Gly Lys Ser Glu SerGlu Leu Pro 305 310 315 His Lys Leu Tyr Val Leu Leu Phe Ala Lys Phe PhePhe Leu Ile 320 325 330 Ser Ile Phe Phe Tyr Asp Val Lys Ile Leu Ala LeuIle Met Tyr 335 340 345 Ile Ala <210> SEQ ID NO 48 <211> LENGTH: 318<212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:55019501CD1 <400> SEQUENCE: 48 Met Arg Gly Asp Asn His Ser Cys Phe TrpAsp Thr Pro Lys Asp 1 5 10 15 Phe Ile Leu Leu Gly Ile Ser Asp Arg ProTrp Leu Glu Leu Pro 20 25 30 Val Phe Ala Val Leu Leu Val Phe Tyr Ile LeuAla Met Leu Gly 35 40 45 Asn Ile Ser Ile Ile Leu Val Ser Gln Leu Asp ProGln Leu His 50 55 60 Ser Pro Met Tyr Ile Phe Leu Ser His Leu Ser Phe LeuAsp Leu 65 70 75 Cys Tyr Thr Thr Thr Thr Val Pro Gln Met Leu Phe Asn MetGly 80 85 90 Ser Ser Gln Lys Thr Ile Ser Tyr Gly Gly Cys Thr Val Gln Tyr95 100 105 Ala Ile Phe His Trp Leu Gly Cys Thr Glu Cys Val Val Leu Ala110 115 120 Ala Met Ala Leu Asp Arg Tyr Val Ala Ile Cys Glu Pro Leu Arg125 130 135 Tyr Ala Ile Ile Met His Arg Pro Leu Cys Gln Gln Leu Val Ala140 145 150 Met Ala Trp Leu Ser Gly Phe Gly Asn Ser Leu Val Gln Val Ile155 160 165 Leu Thr Val Gln Leu Pro Phe Cys Gly Arg Gln Val Leu Asn Asn170 175 180 Phe Phe Cys Glu Val Pro Ala Met Ile Lys Leu Ser Cys Ala Asp185 190 195 Thr Thr Ala Asn Asp Ala Thr Leu Ala Val Leu Val Ala Phe Phe200 205 210 Val Leu Val Pro Leu Ala Leu Ile Leu Leu Ser Tyr Gly Phe Ile215 220 225 Ala Arg Ala Val Met Arg Ile Gln Ser Ser Arg Gly Arg His Lys230 235 240 Ala Phe Gly Thr Cys Ser Ser His Leu Leu Val Val Ser Leu Phe245 250 255 Tyr Leu Pro Ala Ile Tyr Met Tyr Leu Gln Pro Pro Ser Ser Tyr260 265 270 Ser Gln Glu Gln Gly Lys Phe Ile Ser Leu Phe Tyr Ser Ile Ile275 280 285 Thr Pro Thr Leu Asn Pro Phe Ile Tyr Thr Leu Arg Asn Lys Asp290 295 300 Val Lys Gly Ala Leu Arg Arg Leu Leu Ala Arg Thr Gly Arg Leu305 310 315 Cys Gly Arg <210> SEQ ID NO 49 <211> LENGTH: 2181 <212>TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY:misc_feature <223> OTHER INFORMATION: Incyte ID No: 7485090CB1 <400>SEQUENCE: 49 atgcagaaaa ccaagcaaga tgaggactat gaaagagcca ttggatttagtgtcaaaatg 60 gatgacagtg attctgattt tgcactgact caaggtagca tgatcactccttcatgccaa 120 aaaggatatt ttccctgtgg gaatcttacc aagtgcttac cccgagcttttcactgtgat 180 ggcaaggatg actgtgggaa cggggcggac gaagagaact gtggtgacactagtggatgg 240 gcgaccatat ttggcacagt gcatggaaat gctaacagcg tggccttaacacaggagtgc 300 tttctaaaac agtatccaca atgctgtgac tgcaaagaaa ctgaattggaatgtgtaaat 360 ggtgacttaa agtctgtgcc gatgatttct aacaatgtga cattactgtctcttaagaaa 420 aacaaaatcc acagtcttcc agataaagtt ttcatcaaat acacaaaacttaaaaagata 480 tttcttcagc ataattgcat tagacacata tccaggaaag cattttttggattatgtaat 540 ctgcaaatat tatatctcaa ccacaactgc atcacaaccc tcagacctggaatattcaaa 600 gacttacatc agctaacttg gctaattcta gatgacaatc caataaccagaatttcacag 660 cgcttgttta cgggattaaa ttccttgttt ttcctgtcta tggttaataactacttagaa 720 gctcttccca agcagatgtg tgcccaaatg cctcaactca actgggtggatttggaaggc 780 aatagaataa agtatctcac aaattctacg tttctgtcgt gcgattcgctcacagtgctg 840 gatctgtcta gcaatacgat aacggaacta tcacctcacc tttttaaagacttgaagctt 900 ctacaaaagc tgaacctgtc atccaatcct cttatgtatc ttcacaagaaccagtttgaa 960 agtcttaaac aacttcagtc tctagacctg gaaaggatag agattccaaatataaacaca 1020 cgaatgtttc aacccatgaa gaatctttct cacataccct gttatttcaaaaactttcga 1080 tactgctcct atgctcccca tgtccgaata tgtatgccct tgacggacggcatttcttca 1140 tttgaggacc tcttggctaa caatatcctc agaatatttg tctgggttatagctttcatt 1200 acctgctttg gaaatctttt tgtcattggc atgagatctt tcattaaagctgaaaataca 1260 actcacgcta tgtccatcaa aatcctttgt tgtgctgatt gcctgatgggtgtttacttg 1320 ttctttgttg gcattttcga tataaaatac cgagggcagt atcagaagtatgccttgctg 1380 tggatggaga gcgtgcagtg ccgcctcatg gggttcctgg ccatgctgtccaccgaagtc 1440 tctgttctgc tactgaccta cttgactttg gagaagttcc tggtcattgtcttccccttc 1500 agtaacattc gacctggaaa acggcagacc tcagtcatcc tcatttgcatctggatggcg 1560 ggatttttaa tagctgtaat tccattttgg aataaggatt attttggaaacttttatggg 1620 aaaaatggag tatgtttccc actttattat gaccaaacag aagatattggaagcaaaggg 1680 tattctcttg gaattttcct aggtgtgaac ttgctggctt ttctcatcattgtgttttcc 1740 tatattacta tgttctgttc cattcaaaaa accgccttgc agaccacagaagtaaggaat 1800 tgttttggaa gagaggtggc tgttgcaaat cgtttctttt ttatagtgttctctgatgcc 1860 atctgctgga ttcctgtatt tgtagttaaa atcctttccc tcttccgggtggaaatacca 1920 gacacaatga cttcctggat agtgattttt ttccttccag ttaacagtgctttgaatcca 1980 atcctctata ctctcacaac caactttttt aaggacaagt tgaaacagctgctgcacaaa 2040 catcagagga aatcaatttt caaaattaaa aaaaaaagtt tatctacatccattgtgtgg 2100 atagaggact cctcttccct gaaacttggg gttttgaaca aaataacacttggagacagt 2160 ataatgaaac cagtttccta g 2181 <210> SEQ ID NO 50 <211>LENGTH: 3215 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE:<221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:7474890CB1 <400> SEQUENCE: 50 atggtctgtt cggctgcccc actgctgctcctggccacaa ctcttcccct gctggggtca 60 ccagttgccc aagcatccca acctggacagagtcaggctg gaggggaatc tggatctggg 120 cagctcctgg accaagagaa tggagcaggggagtgtaatg tcaaccacaa ggggaatttc 180 tattgtgctt gcctctctgg ctaccagtggaacaccagca tctgcctcca ttaccctcct 240 tgtcaaagcc tccacaacca ccagccttgtggctgccttg tcttcagcca tcccgaaccc 300 gggtactgcc agttgctgcc acctgtccccgggatcctca acctgaactc ccagctgcag 360 atgcctggtg acacgctgag cctgactctccatctgagcc aggaggccac caacctgagc 420 tggttcctga ggcacccagg gagccccagtcccatcctcc tgcagccagg gacacaggtg 480 tctgtgactt ccagccacgg ccaggctgccctcagcgtct ccaacatgtc ccatcactgg 540 gcaggtgagt acatgagctg cttcgaggcccagggcttca agtggaacct gtatgaggtg 600 gtgagggtgc ccttgaaggc gacagatgtggctcgacttc cataccagct gtccatctcc 660 tgtgccacct cccctggctt ccagctgagctgctgcatcc ccagcacaaa cctggcctac 720 accgcggcct ggagccctgg agagggcagcaaagcttcct ccttcaacga gtcaggctct 780 cagtgctttg tgctggctgt tcagcgctgcccgatggctg acaccacgta cgcttgtgac 840 ctgcagagcc tgggcctggc tccactcagggtccccatct ccatcaccat catccaggat 900 ggagacatca cctgccctga ggacgcctcggtgctcacct ggaatgtcac caaggctggc 960 cacgtggcac aggccccatg tcctgagagcaagaggggca tagtgaggag gctctgtggg 1020 gctgacggag tctgggggcc ggtccacagcagctgcacag atgcgaggct cctggccttg 1080 ttcactagaa ccaagctgct gcaggcaggccagggcagtc ctgctgagga ggtgccacag 1140 atcctggcac agctgccagg gcaggcggcagaggcaagtt caccctccga cttactgacc 1200 ctgctgagca ccatgaaata cgtggccaaggtggtggcag aggccagaat acagcttgac 1260 cgcagagccc tgaagaatct cctgattgccacagacaagg tcctagatat ggacaccagg 1320 tctctgtgga ccctggccca agcccggaagccctgggcag gctcgactct cctgctggct 1380 gtggagaccc tggcatgcag cctgtgcccacaggaccacc ccttcgcctt cagcttaccc 1440 aatgtgctgc tgcagagcca gctgtttggacccacgtttc ctgctgacta cagcatctcc 1500 ttccctactc ggcccccact gcaggctcagattcccaggc actcactggc cccattggtc 1560 cgtaatggaa ctgaaataag tattactagcctggtgctgc gaaaactgga ccaccttctg 1620 ccctcaaact atggacaagg gctgggggattccctctatg ccactcctgg cctggtcctt 1680 gtcatttcca tcatggcagg tgaccgggccttcagccagg gagaggtcat catggacttt 1740 gggaacacag atggttcccc tcactgtgtcttctgggatc acagtctctt ccagggcagg 1800 gggggttggt ccaaagaagg gtgccaggcacaggtggcca gtgccagccc cactgctcag 1860 tgcctctgcc agcacctcac tgccttctccgtcctcatgt ccccacacac tgttccggaa 1920 gaacccgctc tggcgctgct gactcaagtgggcttgggag cttccatact ggcgctgctt 1980 gtgtgcctgg gtgtgtactg gctggtgtggagagtcgtgg tgcggaacaa gatctcctat 2040 ttccgccacg ccgccctgct caacatggtgttctgcttgc tggctgcaga cacttgcttc 2100 ctgggcgccc cattcctctc tccagggccccgaagcccgc tctgccttgc tgccgccttc 2160 ctctgtcatt tcctctacct ggccacctttttctggatgc tggcgcaggc cctggtgttg 2220 gcccaccagc tgctctttgt ctttcaccagctggcaaagc accgagttct ccccctcatg 2280 gtgctcctgg gctacctgtg cccactggggttggcaggtg tcaccctggg gctctaccta 2340 cctcaagggc aatacctgag ggagggggaatgctggttgg atgggaaggg aggggcgtta 2400 tacaccttcg tggggccagt gctggccatcataggcgtga atgggctggt actagccatg 2460 gccatgctga agttgctgag accttcgctgtcagagggac ccccagcaga gaagcgccaa 2520 gctctgctgg gggtgatcaa agccctgctcattcttacac ccatctttgg cctcacctgg 2580 ggggctgggc ctggccactc tgttagaggaagtctccacg gtccctcatt acatcttcac 2640 cattctcaac accctccagg gcgtcttcatcctattgttt ggttgcctca tggacaggaa 2700 gatacaagaa gctttgcgca aacgcttctgccgcgcccaa gcccccagct ccaccatctc 2760 cctggccaca aatgaaggct gcatcttggaacacagcaaa ggaggaagcg acactgccag 2820 gaagacagat gcttcagagt gaaccacacacggacccatg ttcctgcaag ggagttgagg 2880 ctgtgtgctt gaacccacca gatgagcctggcccatgctc tgaactcttc ccgcctcccg 2940 gagctcagcc cttgagaaag gcaggcttatatttccctta gtgacactca tttatcttac 3000 agctcacccc ttctcatttc taaagtatccagcaagaata gcaggaaaaa ttagctaaag 3060 gcacctaatg aataagcctg cctttgctccagaaataatc gacagatatc aaagtgcgga 3120 ataattacaa gtaaactttc tcaaccagtttttaactaca acatacatgt cgtgaatgaa 3180 tatatttgat aaaaatggtt ttaattgacccaaaa 3215 <210> SEQ ID NO 51 <211> LENGTH: 1671 <212> TYPE: DNA <213>ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 7474936CB1 <400> SEQUENCE: 51gctcttcagt gaggtgggct cagggagggc tctgtgcctc cgttcagcag agctgcagct 60gctgcccagc tctcaggagg caagctggac tccctcactc ggctgcagga gcaaggacag 120tgaggctcaa ccccgcctga gccatgccag ccaacttcac agagggcagc ttcgattcca 180gtgggaccgg gcagacgctg gattcttccc cagtggcttg cactgaaaca gtgactttta 240ctgaagtggt ggaaggaaag gaatggggtt ccttctacta ctcctttaag actgagcaat 300tgataactct gtgggtcctc tttgttttta ccattgttgg aaactccgtt gtgctttttt 360ccacatggag gagaaagaag aagtcaagaa tgaccttctt tgtgactcag ctggccatca 420cagattcttt cacaggactg gtcaacatct tgacagatat tatttggcga ttcactggag 480acttcacggc acctgacctg gtttgccgag tggtccgcta tttgcaggtt gtgctgctgt 540acgcctctac ctacgtcctg gtgtccctca gcatagacag ataccatgcc atcgtctacc 600ccatgaagtt ccttcaagga gaaaagcaag ccagggtcct cattgtgatc gcctggagcc 660tgtcttttct gttctccatt cccaccctga tcatatttgg gaagaggaca ctgtccaacg 720gtgaagtgca gtgctgggcc ctgtggcctg acgactccta ctggacccca tacatgacca 780tcgtggcctt cctggtgtac ttcatccctc tgacaatcat cagcatcatg tatggcattg 840tgatccgaac tatttggatt aaaagcaaaa cctacgaaac agtgatttcc aactgctcag 900atgggaaact gtgcagcagc tataaccgag gactcatctc aaaggcaaaa atcaaggcta 960tcaagtatag catcatcatc attcttgcct tcatctgctg ttggagtcca tacttcctgt 1020ttgacatttt ggacaatttc aacctccttc cagacaccca ggagcgtttc tatgcctctg 1080tgatcattca gaacctgcca gcattgaata gtgccatcaa ccccctcatc tactgtgtct 1140tcagcagctc catctctttc ccctgcaggg agcgaagatc acaggattcc agaatgacgt 1200tccgggagag aaccgagagg catgagatgc agattctgtc caagccagaa ttcatctaga 1260ccctagggca gtgccagtgc taggctgagc accatcagct ctcccaggtc cttgtcacct 1320gcttgggcac gtgcatggaa cccgagccaa cttcacccca ccctcgtcat tacctgggag 1380atgcacaaga caaatgttct aatgactgca tgcactgctt aagtattggc caacacgaac 1440tccccagtta ttcatgccag ccaggaagga aacgccttcc ttccccacca ttcccagccc 1500tccttcccac tggccagcac ctgaacccag tgaacacagg catcagtggt ccagggtcct 1560ggcttggagc cagtgagtag acaggcaagc agaggggaca aaggtagctg ggttatacat 1620gaatattctc attacaatag aagaaaataa aagacttaat taagccaaaa a 1671 <210> SEQID NO 52 <211> LENGTH: 1336 <212> TYPE: DNA <213> ORGANISM: Homo sapiens<220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION:Incyte ID No: 90012430CB1 <400> SEQUENCE: 52 cctgctgttg aaacagaatcctatttggaa ggcagacatg tggcccatct ctgtagccat 60 cactgagaaa tctggattttcaagcaatga ttttcaacaa ttataaaatg gaagttgtag 120 actggataag agatgctcagctaagggagt tcctggatgg tctttagatt gatacaccaa 180 tcctctgaaa ttgcatgcaaaaatgtgact tcccaagtat gcctggccac aatacctcca 240 ggaattcctc ttgcgatcctatagtgacac cccacttaat cagcctctac ttcatagtgc 300 ttattggcgg gctggtgggtgtcatttcca ttcttttcct cctggtgaaa atgaacaccc 360 ggtcagtgac caccatggcggtcattaact tggtggtggt ccacagcgtt tttctgctga 420 cagtgccatt tcgcttgacctacctcatca agaagacttg gatgtttggg ctgcccttct 480 gcaaatttgt gagtgccatgctgcacatcc acatgtacct cacgttccta ttctatgtgg 540 tgatcctggt caccagatacctcatcttct tcaagtgcaa agacaaagtg gaattctaca 600 gaaaactgca tgctgtggctgccagtgctg gcatgtggac gctggtgatt gtcattgtgg 660 tacccctggt tgtctcccggtatggaatcc atgaggaata caatgaggag cactgtttta 720 aatttcacaa agagcttgcttacacatatg tgaaaatcat caactatatg atagtcattt 780 ttgtcatagc cgttgctgtgattctgttgg tcttccaggt cttcatcatt atgttgatgg 840 tgcagaagct acgccactctttactatccc accaggagtt ctgggctcag ctgaaaaacc 900 tattttttat aggggtcatccttgtttgtt tccttcccta ccagttcttt aggatctatt 960 acttgaatgt tgtgacgcattccaatgcct gtaacagcaa ggttgcattt tataacgaaa 1020 tcttcttgag tgtaacagcaattagctgct atgatttgct tctctttgtc tttgggggaa 1080 gccattggtt taagcaaaagataattggct tatggaattg tgttttgtgc cgttagccac 1140 aaactacagt attcatatttgcttccttta tattgggaat aaaaatgggt ataggggagg 1200 taagaatggt atttcattacttgatcaaaa ccatgccttg atgtacccaa aacaaaagga 1260 ctataaaatg caagagccctcattgtagtc cttatgggat ccctcccatc tctgagtgat 1320 ggcgtacaag acccgt 1336<210> SEQ ID NO 53 <211> LENGTH: 1340 <212> TYPE: DNA <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 90012586CB1 <400> SEQUENCE: 53 cctgctgttgaaacagaatc ctatttggaa ggcagacatg tggcccatct ctgtagccat 60 cactgagaaatctggatttt caagggcctt tctctctgtt gcccaggctg gagtttagcg 120 actcaatcatggctcactga ctgcagcatc gacctccggg gctcaagtga tcctttcatc 180 tcagcctcctcagtagctga gactacaggt gacttcccaa gtatgcctgg ccacaatacc 240 tccaggaattcctcttgcga tcctatagtg acaccccact taatcagcct ctacttcata 300 gtgcttattggcgggctggt gggtgtcatt tccattcttt tcctcctggt gaaaatgaac 360 acccggtcagtgaccaccat ggcggtcatt aacttggtgg tggtccacag cgtttttctg 420 ctgacagtgccatttcgctt gacctacctc atcaagaaga cttggatgtt tgggctgccc 480 ttctgcaaatttgtgagtgc catgctgcac atccacatgt acctcacgtt cctattctat 540 gtggtgatcctggtcaccag atacctcatc ttcttcaagt gcaaagacaa agtggaattc 600 tacagaaaactgcatgctgt ggctgccagt gctggcatgt ggacgctggt gattgtcatt 660 gtggtacccctggttgtctc ccggtatgga atccatgagg aatacaatga ggagcactgt 720 tttaaatttcacaaagagct tgcttacaca tatgtgaaaa tcatcaacta tatgatagtc 780 atttttgtcatagccgttgc tgtgattctg ttggtcttcc aggtcttcat cattatgttg 840 atggtgcagaagctacgcca ctctttacta tcccaccagg agttctgggc tcagctgaaa 900 aacctattttttataggggt catccttgtt tgtttccttc cctaccagtt ctttaggatc 960 tattacttgaatgttgtgac gcattccaat gcctgtaaca gcaaggttgc attttataac 1020 gaaatcttcttgagtgtaac agcaattagc tgctatgatt tgcttctctt tgtctttggg 1080 ggaagccattggtttaagca aaagataatt ggcttatgga attgtgtttt gtgccgttag 1140 ccacaaactacagtattcat atttgcttcc tttatattgg gaataaaaat gggtataggg 1200 gaggtaagaatggtatttca ttacttgatc aaaaccatgc cttgatgtac ccaaaacaaa 1260 aggactataaaatgcaagag ccctcattgt agtccttatg ggatccctcc catctctgag 1320 tgatggcgtacaagacccgt 1340 <210> SEQ ID NO 54 <211> LENGTH: 1460 <212> TYPE: DNA<213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature<223> OTHER INFORMATION: Incyte ID No: 90012670CB1 <400> SEQUENCE: 54cctgctgttg aaacagaatc ctatttggaa ggcagacatg tggcccatct ctgtagccat 60cactgagaaa tctggatttt caagcaatga ttttcaacaa ttataaaatg gaagttgtag 120attggataag agatgctcag ctaagggagt tcctggatgg tctttagatt gatacaccaa 180tcctctgaaa ttgcatgcaa aaatggcctt tctctctgtt gcccaggctg gagtttagcg 240actcaatcat ggctcactga ctgcagcatc gacctccggg gctcaagtga tcctttcatc 300tcagcctcct cagtagctga gactacaggt gacttcccaa gtatgcctgg ccacaatacc 360tccaggaatt cctcttgcga tcctatagtg acaccccact taatcagcct ctacttcata 420gtgcttattg gcgggctggt gggtgtcatt tccattcttt tcctcctggt gaaaatgaac 480acccggtcag tgaccaccat ggcggtcatt aacttggtgg tggtccacag cgtttttctg 540ctgacagtgc catttcgctt gacctacctc atcaagaaga cttggatgtt tgggctgccc 600ttctgcaaat ttgtgagtgc catgctgcac atccacatgt acctcacgtt cctattctat 660gtggtgatcc tggtcaccag atacctcatc ttcttcaagt gcaaagacaa agtggaattc 720tacagaaaac tgcatgctgt ggctgccagt gctggcatgt ggacgctggt gattgtcatt 780gtggtacccc tggttgtctc ccggtatgga atccatgagg aatacaatga ggagcactgt 840tttaaatttc acaaagagct tgcttacaca tatgtgaaaa tcatcaacta tatgatagtc 900atttttgtca tagccgttgc tgtgattctg ttggtcttcc aggtcttcat cattatgttg 960atggtgcaga agctacgcca ctctttacta tcccaccagg agttctgggc tcagctgaaa 1020aacctatttt ttataggggt catccttgtt tgtttccttc cctaccagtt ctttaggatc 1080tattacttga atgttgtgac gcattccaat gcctgtaaca gcaaggttgc attttataac 1140gaaatcttct tgagtgtaac agcaattagc tgctatgatt tgcttctctt tgtctttggg 1200ggaagccatt ggtttaagca aaagataatt ggcttatgga attgtgtttt gtgccgttag 1260ccacaaacta cagtattcat atttgcttcc tttatattgg gaataaaaat gggtataggg 1320gaggtaagaa tggtatttca ttacttgatc aaaaccatgc cttgatgtac ccaaaacaaa 1380aggactataa aatgcaagag ccctcattgt agtccttatg ggatccctcc catctctgag 1440tgatggcgta caagacccgt 1460 <210> SEQ ID NO 55 <211> LENGTH: 4052 <212>TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY:misc_feature <223> OTHER INFORMATION: Incyte ID No: 2880041CB1 <400>SEQUENCE: 55 gaaagattgg acctccgaaa caatcttatt agtagtatag atccaggtgccttctgggga 60 ctgtcatctc taaaaagatt ggatctgaca aacaatcgaa taggatgtctgaatgcagac 120 atatttcgag gactcaccaa tctggttcgg ctaaaccttt cggggaatttgttttcttca 180 ttatctcaag gaacttttga ttatcttgcg tcattacggt ctttggaattccagactgag 240 tatcttttgt gtgactgtaa catactgtgg atgcatcgct gggtaaaggagaagaacatc 300 acggtacggg ataccaggtg tgtttatcct aagtcactgc aggcccaaccagtcacaggc 360 gtgaagcagg agctgttgac atgcgaccct ccgcttgaat tgccgtctttctacatgact 420 ccatctcatc gccaagttgt gtttgaagga gacagccttc ctttccagtgcatggcttca 480 tatattgatc aggacatgca agtgttgtgg tatcaggatg ggagaatagttgaaaccgat 540 gaatcgcaag gtatttttgt tgaaaagaac atgattcaca actgctccttgattgcaagt 600 gccctaacca tttctaatat tcaggctgga tctactggaa attggggctgtcatgtccag 660 accaaacgtg ggaataatac gaggactgtg gatattgtgg tattagagagttctgcacag 720 tactgtccgc cagagagggt ggtaaacaac aaaggtgact tcagatggcccagaacattg 780 gcaggcatta ctgcatatct gcagtgtacg cggaacaccc atggcagtgggatatatccc 840 ggaaacccac aggatgagag aaaagcttgg cgcagatgtg atagaggtggcttttgggca 900 gatgatgatt attctcgctg tcagtatgca aatgatgtca ctagagttctttatatgttt 960 aatcagatgc ccctcaatct taccaatgcc gtggcaacag ctcgacagttactggcttac 1020 actgtggaag cagccaactt ttctgacaaa atggatgtta tatttgtggcagaaatgatt 1080 gaaaaatttg gaagatttac caaggaggaa aaatcaaaag agctaggtgacgtgatggtt 1140 gacattgcaa gtaacatcat gttggctgat gaacgtgtcc tgtggctggcgcagagggaa 1200 gctaaagcct gcagtaggat tgtgcagtgt cttcagcgca ttgctacctaccggctagcc 1260 ggtggagctc acgtttattc aacatattca cccaatattg ctctggaagcttatgtcatc 1320 aagtctactg gcttcacggg gatgacctgt accgtgttcc agaaagtggcagcctctgat 1380 cgtacaggac tttcggatta tgggaggcgg gatccagagg gaaacctggataagcagctg 1440 agctttaagt gcaatgtttc aaatacattt tcgagtctgg cactaaagaatactattgtg 1500 gaggcttcta ttcagcttcc tccttccctt ttctcaccaa agcaaaaaagagaactcaga 1560 ccaactgatg actctcttta caagcttcaa ctcattgcat tccgcaatggaaagcttttt 1620 ccagccactg gaaattcaac aaatttggct gatgatggaa aacgacgtactgtggttacc 1680 cctgtgattc tcaccaaaat agatggtgtg aatgtagata cccaccacatccctgttaat 1740 gtgacactgc gtcgaattgc acatggagca gatgctgttg cagcccggtgggatttcgat 1800 ttgctgaacg gacaaggagg ctggaagtca gatgggtgcc atatactctattcagatgaa 1860 aatatcacta cgattcagtg ctactccctt agtaactatg cagttttaatggatttgacg 1920 ggatctgaac tatacaccca ggcggccagc ctcctgcatc ctgtggtttatactaccgct 1980 atcattctcc tcttatgtct cttagccgtc attgtcagtt acatataccatcacagtttg 2040 attagaatca gcctcaagag ctggcacatg cttgtgaact tgtgctttcatattttccta 2100 acctgtgtgg tctttgtggg aggaataacc cagactagga atgccagcatctgccaagca 2160 gttgggataa ttcttcacta ttccaccctt gccacagtac tatgggtaggagtgacagct 2220 cgaaatatct acaaacaagt cactaaaaaa gctaaaagat gccaggatcctgatgaacca 2280 ccacctccac caagaccaat gctcagattt tacctgattg gtggtggtatccccatcatt 2340 gtttgcggca taactgcagc agcgaacatt aagaattacg gcagtcggccaaacgcaccc 2400 tattgctgga tggcatggga accctccttg ggagccttct atgggccagccagcttcatc 2460 acttttgtaa actgcatgta ctttctgagc atatttattc agttgaaaagacaccctgag 2520 cgcaaatatg agcttaagga gcccacggag gagcaacaga gattggcagccaatgaaaat 2580 ggcgaaataa atcatcagga ttcaatgtct ttgtctctga tttctacatcagccttggaa 2640 aatgagcaca cttttcattc tcagctcttg ggggccagcc ttactttgctcttatatgtt 2700 gcactgtgga tgtttggggc tttggctgtt tctttgtatt accctttggacttggttttt 2760 agcttcgttt ttggagccac aagtttaagc ttcagtgcgt tcttcatggtccaccattgt 2820 gttaataggg aggatgttag acttgcgtgg atcatgactt gctgcccaggacggagctcg 2880 tattcagtgc aagtcaacgt ccagcccccc aactctaatg ggacgaatggagaggcaccc 2940 aaatgcccca atagcagtgc ggagtcttca tgcacaaaca aaagtgcttcaagcttcaaa 3000 aattcctccc agggctgcaa attaacaaac ttgcaggcgg ctgcagctcagtgccatgcc 3060 aattctttac ctttgaactc cacccctcag cttgataata gtctgacagaacattcaatg 3120 gacaatgata ttaaaatgca cgtggcgcct ttagaagttc agtttcgaacaaatgtgcac 3180 tcaagccgcc accataaaaa cagaagtaaa ggacaccggg caagccgactcacagtcctg 3240 agagaatatg cctacgatgt cccaacgagc gtggaaggaa gcgtgcagaacggcttacct 3300 aaaagccggc tgggcaataa cgaaggacac tcgaggagcc gaagagcttatttagcctac 3360 agagagagac agtacaaccc accccagcaa gacagcagcg atgcttgtagcacacttccc 3420 aaaagtagca gaaattttga aaagccagtt tcaaccacta gtaaaaaagatgcgttaagg 3480 aagccagctg tggttgaact tgaaaatcag caaaaatctt atggcctcaacttggccatt 3540 cagaatggac caattaaaag caatgggcag gagggaccct tgctcggtaccgatagcact 3600 ggcaatgtta ggactggatt atggaaacac gaaactactg tgtaacattgctgggcttcc 3660 taggcagaaa ttcatataaa ctgtgatact cacattcctt gaagctatgagcatttaaaa 3720 actgtttaca gccaccatag ggattcaaaa gaatttggaa taaactttgaagttttggat 3780 tttacttatt tttatcccca aattgttgct attttttagg atctgaaacaaaatctttct 3840 aaaacattgt tttagttgtc aaagcaccaa caggacattt tgggatgtgaaatgtaattt 3900 cttggaatct gtaatttgta cttaatattt caggctgtat ttatatataataaataggtg 3960 ttgttattgt caaacaaaaa aagggcggcc ccgatagtga gcccgcgaccggaatatccg 4020 ccggccgcag cgggcgggat cgatagcttc ac 4052 <210> SEQ ID NO56 <211> LENGTH: 1142 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 90012123CB1 <400> SEQUENCE: 56 agcactacag cctaagcttc cagagtggacacggagaagg gcatcagaaa accattctgg 60 tgaggtccac acccataagt caccatgtacaaggactgca tcgagtccac tggagactat 120 tttcttctct gtgacgccga ggggccatggggcatcattc tggagtccct ggccatactt 180 ggcatcgtgg tcacaattct gctactcttagcatttctct tcctcatgcg aaagatccaa 240 gactgcagcc agtggaatgt cctccccacccagctcctct tcctcctgag tgtcctgggg 300 ctcttcggac tcgcttttgc cttcatcatcgagctcaatc aacaaactgc ccccgtacgc 360 tactttctct ttggggttct ctttgctctctgtttctcat gcctcttagc tcatgcctcc 420 aatctagtga agctggttcg gggttgtgtctccttctcct ggacgacaat tctgtgcatt 480 gctattggtt gcagtctgtt gcaaatcattattgccactg agtatgtgac tctcatcatg 540 accagaggta tgatgtttgt gaatatgacaccctgccagc tcaatgtgga ctttgttgta 600 ctcctggtct atgtcctctt cctgatggccctcacattct tcgtctccaa agccaccttc 660 tgtggcccgt gtgagaactg gaagcagcatggaaggctca tctttatcac tgtgctcttc 720 tccatcatca tctgggtggt gtggatctccatgctcctga gaggcaaccc gcagttccag 780 cgacagcccc agtgggatga cccggtcgtctgcattgctc tggtcaccaa cgcatgggtt 840 ttcctgctgc tgtacatcgt ccctgagctctgcattccct acagatcgtg tagacaggag 900 tgccctttac aaggcaatgc ctgccccgtcacagcctacc aacacagctt ccaagtggag 960 aaccaggagc tctccagagc ccgagacagtgatggagctg aggaggatgt agcattaact 1020 tcatatggta ctcccattca gccgcagactgttgatccca cacaagagtg tttcatccca 1080 caggctaaac taagccccca gcaagatgcaggaggagtat aaaagagcga attccagcac 1140 ac 1142 <210> SEQ ID NO 57 <211>LENGTH: 1054 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE:<221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:90012163CB1 <400> SEQUENCE: 57 agcactacag cctaagcttc cagagtggacacggagaagg gcatcagaaa accattctgg 60 tgaggtccac acccataagt caccatgtacaaggactgca tcgagtccac tggagactat 120 tttcttctct gtgacgccga ggggccatggggcatcattc tggagtccct ggccatactt 180 ggcatcgtgg tcacaattct gctactcttagcatttctct tcctcatgcg aaagatccaa 240 gactgcagcc agtggaatgt cctccccacccagctcctct tcctcctgag tgtcctgggg 300 ctcttcggac tcgcttttgc cttcatcatcgagctcaatc aacaaactgc ccccgtacgc 360 tactttctct ttggggttct ctttgctctctgtttctcat gcctcttagc tcatgcctcc 420 aatctagtga agctggttcg gggttgtgtctccttctcct ggacgacaat tctgtgcatt 480 gctattggtt gcagtctgtt gcaaatcattattgccactg agtatgtgac tctcatcatg 540 accagaggta tgatgtttgt gaatatgacaccctgccagc tcaatgtgga ctttgttgta 600 ctcctggtct atgtcctctt cctgatggccctcacattct tcgtctccaa agccaccttc 660 tgtggcccgt gtgagaactg gaagcagcatggaaggctca tctttatcac tgtgctcttc 720 tccatcatca tctgggtggt gtggatctccatgctcctga gaggcaaccc gcagttccag 780 cgacagcccc agtgggatga cccggtcgtctgcattgctc tggtcaccaa cgcatgggtt 840 ttcctgctgc tgtacatcgt ccctgagctctgcattctct acagatcgtg tagacaggag 900 tgccctttac aaggcaatgc ctgccccgtcacagcctacc aacacagctt ccaagtggag 960 aaccaggagc tctccagaga ctgttgatcccacacaagag tgtttcatcc cacaggctaa 1020 actaagcccc cagcaagatg caggaggagtataa 1054 <210> SEQ ID NO 58 <211> LENGTH: 1251 <212> TYPE: DNA <213>ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 7472462CB1 <400> SEQUENCE: 58cctataccat tacctctagc acactgataa gagtctttct gtttcttcag gaacttgaca 60agagaggacc ttaaagaaag tgagatcctt catacttagg aattcagtga cacttgctgg 120gagaatgcct tctatcaatg acacccactt ctatcccccc ttcttcctcc tgctaggaat 180accaggactg gacactttac atatctggat ttctttccca ttctgtattg tgtacctgat 240tgccattgtg gggaatatga ccattctctt tgtgatcaaa actgaacata gtctacacca 300gcccatgttc tacttcctgg ccatgttgtc tatgattgat ctgggtctgt ccacatccac 360tatccccaaa atgctaggaa tcttctggtt caacctccaa gagatcagct ttgggggatg 420ccttcttcag atgttcttta ttcacatgtt tacaggcatg gagactgttc tgttggtggt 480catggcttat gaccgctttg ttgccatctg caaccctctc cagtacacca tgatcctcac 540caataaaacc atcagtatcc tagcttctgt ggttgttgga agaaatttag ttcttgtaac 600cccatttgtg tttctcattc tgcgtctgcc attctgtggg cataacatcg tacctcacac 660atactgtgag cacaggggtc tggccgggtt ggcctgtgca cccattaaga tcaacataat 720ctatgggctc atggtgattt cttatattat tgtggatgtg atcttaattg cctcttccta 780tgtgcttatc cttagagctg tttttcgcct tccctctcaa gatgtccgac taaaggcctt 840caatacctgt ggttctcatg tctgtgttat gctgtgcttt tacacaccag catttttttc 900ttttatgaca catcgttttg gccaaaacat tccccactat atccatattc ttttggctaa 960cctgtatgtg gttgtcccac ctgcccttaa ccctgtcatt tatggagtca ggaccaagca 1020gatccgagag caaattgtga aaatatttgt acagaaagaa taattctgta ttaaagtttg 1080gataaatata tctatataca acccaaatta tcatcatctg agctcccttt ttaatcttct 1140gtaacagttg gtcatgcttg tcagattttt tccttttgac tggaagtgct ttagtgttga 1200cagataatgc aaacttaaaa cctttgctgc ctgtttcccc tacttctctc c 1251 <210> SEQID NO 59 <211> LENGTH: 1187 <212> TYPE: DNA <213> ORGANISM: Homo sapiens<220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION:Incyte ID No: 7474873CB1 <400> SEQUENCE: 59 aaagacatag cttctaagcatttaacatac aatacttttt tgggtaggca ggtgacattg 60 tcactcattt aaccctatgtgatgtgttat ctttctcagc tatgcctcag ccttggggaa 120 cacactttac atatggggatggtgagacat accaatgaga gcaacctagc aggtttcatc 180 cttttagggt tttctgattatcctcagtta cagaaggttc tatttgtgct catattgatt 240 ctgtatttac taactattttggggaatacc accatcattc tggtttctcg tctggaaccc 300 aagcttcata tgccgatgtatttcttcctt tctcatctct ccttcctgta ccgctgcttc 360 accagcagtg ttattccccagctcctggta aacctgtggg aacccatgaa aactatcgcc 420 tatggtggct gtttggttcacctttacaac tcccatgccc tgggatccac tgagtgcgtc 480 ctcccggctg tgatgtcctgtgaccgctat gtggctgtct gccgtcctct ccattacact 540 gtcttaatgc atatccatctctgcatggcc ttggcatcta tggcatggct cagtggaata 600 gccaccaccc tggtacagtccaccctcacc ctgcagctgc ccttctgtgg gcatcgccaa 660 gtggatcatt tcatctgcgaggtccctgtg ctcatcaagc tggcttgtgt gggcaccacg 720 tttaacgagg ctgagctttttgtggctagt atccttttcc ttatagtgcc tgtctcattc 780 atcctggtct cctctggctacattgcccac gcagtgttga ggattaagtc agctaccagg 840 agacagaaag cattcgggacctgcttctcc cacctgacag tggtcaccat cttttatgga 900 accatcatct tcatgtatctgcagccagcc aagagtagat ccagggacca gggcaagttt 960 gtttctctct tctacactgtggtaacccgc atgcttaacc ctcttattta taccttgagg 1020 atcaaggagg tgaaaggggcattaaagaaa gttctagcaa aggctctggg agtaaatatt 1080 ttatgattat taaaaaaaaatttaagtgac actgtgatga attttttttt tggtaaaaag 1140 tagcatcttt taataagaggattttttatg ggctcttctc acatttt 1187 <210> SEQ ID NO 60 <211> LENGTH: 1201<212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7475172CB1<400> SEQUENCE: 60 gggaggatgc atcagcagag agcccaggat gtttcactagcaccaaaggc tcaagactag 60 ccgtccaaga ttagcctttt aatggggttc ttgtctcccatgcatccctg caggcctccc 120 acccagagga gaatggctgc aggaaatcac tctacagtgacagagttcat tctcaagggt 180 ttaacgaaga gagcagacct ccagctcccc ctctttctcctcttcctcgg gatctacttg 240 gtcaccatcg tggggaacct gggcatgatc actctaatttgtctgaactc tcagctgcac 300 acccccatgt actactttct cagcaatctg tcactcatggatctctgcta ctcctccgtc 360 attaccccta agatgctggt gaactttgtg tcagagaaaaacatcatctc ctacgcaggg 420 tgcatgtcac agctctactt cttccttgtt tttgtcattgctgagtgtta catgctgaca 480 gtgatggcct acgaccgcta tgttgccatc tgccaccctttgctttacaa catcattatg 540 tctcatcaca cctgcctgct gctggtggct gtggtctacgccatcggact cattggctcc 600 acaatagaaa ctggcctcat gttaaaactg ccctattgtgagcacctcat cagtcactac 660 ttctgtgaca tcctccctct catgaagctg tcctgctctagcacctatga tgttgagatg 720 acagtcttct tttcggctgg attcaacatc atagtcacgagcttaacagt tcttgtttct 780 tacaccttca ttctctccag catcctcggc atcagcaccacagaggggag atccaaagcc 840 ttcagcacct gcagctccca ccttgcagcc gtgggaatgttctatggatc aactgcattc 900 atgtacttaa aaccctccac aatcagttcc ttgacccaggagaatgtggc ctctgtgttc 960 tacaccacgg taatccccat gttgaatccc ctaatctacagcctgaggaa caaggaagta 1020 aaggctgccg tgcagaaaac gctgaggggt aaactgttttgatgcaaatg ttattgttcc 1080 ttttcaattt agtggtaatt gttataaata ccagagtgacagcttctgaa tgctggccag 1140 ctgtggatgg aaaataatca cttctccaca tggctgggtgaatgggcatt tttccttctt 1200 t 1201 <210> SEQ ID NO 61 <211> LENGTH: 2436<212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7475259CB1<400> SEQUENCE: 61 gtaccgatga tgaataatga tgcagcttta ctactgagaagggccccgtg cgtacagcaa 60 caaagtagtc actctgtctg gcttttatta gccacttagcacctattttc ttgtattttg 120 ttatagccct gtgtttcctt ctctgtcctt ccatattctctataatgact actcagcacg 180 attattcaat tgcttagaaa agaaaaacac aggaaggacagagaagtgga tattttagtc 240 agaagaaaac tccaatatct tacacttttc cccttggaagctctgccttt ctgtggcgca 300 ctgttgcttg tttccttcca aagcctgcct ctcctatctaccttcctcac agtttaaggt 360 gcaaggcaga ggcatccttt aaaaattaat tttcctagtctgacaggaga atttcttgaa 420 cccgggaggc ggaggttgtg gtgaggcaag attgagtcattgcactccag cctgggcaat 480 aagagcaagg ctccatctca aaaaataata ataataattaattttcctag tctgaaatgc 540 atttatttgt atctgctttt gacctattga agaaaccatgtcagctttct cacctcacac 600 ccgggacaga cagacgttaa aaaatgacca aacctacagaaaatatttcc agataatgaa 660 atttgagtat tgctttgctt tttgcacatc agttgaagatgtttactaga aaaaaaaaag 720 gtcattcagg ggtccaacag caagtatttc agatgattttggcatggagg taaagcttaa 780 gagatatttc taactggttt cttcaggatt ccagaatcagcttgagtaac tcattacaga 840 aaggaatgaa gcaatattca gtgggtaatc aacattccaattataggagt ctcttgtttc 900 cttttctgtg ttcacagatg acacagttga cggccagtgggaatcagaca atggtgactg 960 agttcctctt ctctatgttc ccgcatgcgc acagaggtggcctcttattc tttattccct 1020 tgcttctcat ctacggattt atcctaactg gaaacctaataatgttcatt gtcatccagg 1080 tgggcatggc cctgcacacc cctttgtatt tctttatcagtgtcctctcc ttcctggaga 1140 tctgctatac cacaaccacc atccccaaga tgctgtcctgcctaatcagt gagcagaaga 1200 gcatttccgt ggctggctgc ctcctgcaga tgtactttttccactcactt ggtatcacag 1260 aaagctgtgt cctgacagca atggccattg acaggtacatagctatctgc aatccactcc 1320 gttacccaac catcatgatt cccaaacttt gtatccagctgacagttgga tcctgctttt 1380 gtggcttcct ccttgtgctt cctgagattg catggatttccaccttgcct ttctgtggct 1440 ccaaccagat ccaccagata ttctgtgatt tcacacctgtgctgagcttg gcctgcacag 1500 atacattcct agtggtcatt gtggatgcca tccatgcagcggaaattgta gcctccttcc 1560 tggtcattgc tctatcctac atccggatta ttatagtgattctgggaatg cactcagctg 1620 aaggtcatca caaggccttt tccacctgtg ctgctcaccttgctgtgttc ttgctatttt 1680 ttggcagtgt ggctgtcatg tatttgagat tctcagccacctactcagtg ttttgggaca 1740 cagcaattgc tgtcactttt gttatccttg ctccctttttcaaccccatc atctatagcc 1800 tgaaaaacaa ggacatgaaa gaggctattg gaaggcttttccactatcag aagagggctg 1860 gttgggctgg gaaatagata cagatcctgg agactctaaaaagcctcttg gaagagcaaa 1920 atttcactgt tatttatctt ttccatgtct atcctctttctgtattgctg caactacttg 1980 ttctattatt tttaaaaaga atgataaact gctgtatacaggctgtggat ggtaagtgga 2040 tggccagttt acatcaatgc ctctaccatg cttgttatagctgaagcagt atagatcaac 2100 tctcttgctt ttaacacagg ttggcttcct cctcgcactccagcagctag gcccctgcta 2160 gtctcttcag tgctctgaca tgctagtggg gccgggaagcagaatagaag aggcatgaca 2220 gacaagaaag ttctgagaat tgctactgct aacttccccaattccctttc tggaaatgca 2280 tcccctgtca tttggcattc catataaata aatcgtttcctgatactaga gagaggtctt 2340 ctctactttt agctcattta attcccaaac tcatttcagcaaacgtgaac tgattttgta 2400 catgatgtgt tacagaattt tagaccccaa gaggtt 2436<210> SEQ ID NO 62 <211> LENGTH: 1050 <212> TYPE: DNA <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7475267CB1 <400> SEQUENCE: 62 tatctatctcttgtaggtaa ttcagaccct aatacctgga aggtattact ctctgaatgg 60 atcaccacatgcctcccaac aatgtgactg aattcattct cttggggctc acacagaatc 120 cacacttgcagaaaatactc tttattgtat ttttatttat ttttctattt accatgctgg 180 ccaatctgttcattgtcatc accatctcct gtagccccac actttcatca cccatgtact 240 tctttctcacttacttatcc tttatagatg cctcctacac ctctgtcaca acccccaaaa 300 tgatcaccgacctgctctac cagaggagaa ctatttcctt ggctggctgc ctgactcagc 360 tctttgtggagcacttgctg ggaggctcag agatcatcct ccttattgtc atggcctatg 420 accgctacgtggccatctgc aagcccctgc actacacaac cattatgcaa caagggatct 480 gccaccttctggtggtgata gcctggattg gaggcatcct gcatgccact gtgcagattc 540 ttttcatgaccgacttgccc ttctgtggtc ccaatgtcat tgaccacttt atgtgtgatc 600 tcttcccattgttgaaactt gcctgcagag acacctacag acttgggatg ctggtggcag 660 ccaacagtggagccatgtgc ttgctcatct tttccctgct cgtcatctcc tacatagtca 720 tcctgagctccctgaaatcc tatagctctg aaggacagca caaagccctc tccacctgtg 780 gctcccactttactgtcgtt gtactctttt ttgtgccttg catattcacc tacatgcatc 840 ctgtggtcacctactctgtg gacaagttgg tgactgtgtt ctttgcaatc ctcactccca 900 tgttaaatcctataatttac actgtgagaa acacagaggt aaaaaatgcc gtgaggagtt 960 tgttgaggaaaagagtaaca gtttatgcat aatggcaaga aagtgatgat atatataaac 1020 atggaggattatatctgtgg taaattgtgc 1050 <210> SEQ ID NO 63 <211> LENGTH: 1451 <212>TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY:misc_feature <223> OTHER INFORMATION: Incyte ID No: 7475271CB1 <400>SEQUENCE: 63 tcaagaatta agtccctaag tacacacact cctcatgtta tctcctaacaacacagggat 60 tctttccatt ttcagttgtt tattctgtgc aattactgcc attcaatcacccaagcagga 120 tgaatcacag cgttgtaact gagttcatta ttctgggcct caccaaaaagcctgaactcc 180 agggaattat cttcctcttt tttctcattg tctatcttgt ggcttttctcggcaacatgc 240 tcatcatcat tgccaaaatc tataacaaca ccttgcatac gcccatgtatgttttccttc 300 tgacactggc tgttgtggac atcatctgca caacaagcat cataccgaagatgctgggga 360 ccatgctaac atcagaaaat accatttcat atgcaggctg catgtcccagctcttcttgt 420 tcacatggtc tctgggagct gagatggttc tcttcaccac catggcctatgaccgctatg 480 tggccatttg tttccctctt cattacagta ctattatgaa ccaccatatgtgtgtagcct 540 tgctcagcat ggtcatggct attgcagtca ccaattcctg ggtgcacacagctcttatca 600 tgaggttgac tttctgtggg ccaaacacca ttgaccactt cttctgtgagatacccccat 660 tgctggcttt gtcctgtagc cctgtaagaa tcaatgaggt gatggtgtatgttgctgata 720 ttaccctggc cataggggac tttattctta cctgcatctc ctatggttttatcattgttg 780 ctattctccg tatccgcaca gtagaaggca agaggaaggc cttctcaacatgctcatctc 840 atctcacagt ggtgaccctt tactattctc ctgtaatcta cacctatatccgccctgctt 900 ccagctatac atttgaaaga gacaaggtgg tagctgcact ctatactcttgtgactccca 960 cattaaaccc gatggtgtac agcttccaga atagggagat gcaggcaggaattaggaagg 1020 tgtttgcatt tctgaaacac tagtagtttc aacatgcaac atcacttctgtactccagaa 1080 ccatcttcta gagcatctca gattttactg gtttttcata cttacctccactccaatttt 1140 cccttccctc ttattcctgc cttcttccta gcagtctcat tgtctccaaaattctgtact 1200 ctttatgtga agaatattca taaagcaata tgcacaatac cctcacataaatatatgtca 1260 taatatatat tccaacattt tccaaaaata tgtacataac ttcgaatacttatatatgca 1320 tatacacaaa tatttaccta tatgtgcatg tgcacatcat acatgcaaatatcacaaaac 1380 attttgtgta ttttgtgcca tttatttgtt ggtatgtgaa tgtgagctggagagaagtag 1440 tgtgtgtgat a 1451 <210> SEQ ID NO 64 <211> LENGTH: 1288<212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7475305CB1<400> SEQUENCE: 64 agtgtggctt caggaccagg gtgttggcta tcatgaaatgaggaagcata aacagtagaa 60 gtgatttctt aggttgttga gatagataga ataatataaatgtggcatac cttgtgttta 120 gttcaagaac tataatctag atgtaacacc tgaaaataaactcttttatt gatattctac 180 aggcagaaga aatgaagata gcaaacaaca cagtagtgacagaatttatc ctccttggtc 240 tgactcagtc tcaagatatt cagctcttgg tctttgtgctgatcttaatt ttctacctta 300 tcatcctccc tggaaatttt ctcattattt tcaccataaggtcagaccct gggctcacag 360 cccccctcta tttatttctg ggcaacttgg ccttcctggatgcatcctac tccttcattg 420 tggctcccag gatgttggtg gacttcctct ctgagaaaaaggtaatctcc tacagaggct 480 gcatcactca gctctttttc ttgcacttcc ttggaggaggggagggatta ctccttgttg 540 tgatggcctt tgaccgctac atcgccatct gccggcctctgcactgttca actgtcatga 600 accctagagc ctgctatgca atgatgttgg ctctgtggcttgggggtttt gtccactcca 660 ttatccaggt ggtcctcatc ctccgcttgc ctttttgtggcccaaaccag ctggacaact 720 tcttctgtga tgtccgacag gtcatcaagc tggcttgcaccgacatgttt gtggtggagc 780 ttctaatggt cttcaacagt ggcctgatga cactcctgtgctttctgggg cttctggctt 840 cctatgcagt catcctctgc catgttcgta gggcagcttctgaagggaag aacaaggcca 900 tgtccacgtg caccactcgt gtcattatta tacttcttatgtttggacct gctatcttca 960 tctacatgtg ccctttcagg gccttaccag ctgacaagatggtttctctc tttcacacag 1020 tgatctttcc attgatgaat cctatgattt atacccttcgcaaccaggaa gtgaaaactt 1080 ccatgaagag gttattgagt cgacatgtag tctgtcaagtggattttata ataagaaact 1140 gagaaggagg aattctggct ggaattcata tcattcatttaacaagtcct gtttttcact 1200 gagtacctcc catttgccag gtaccattgt aggcaatggaggagagttat gcataatgag 1260 agaataaact tattatattt aaagaata 1288 <210> SEQID NO 65 <211> LENGTH: 1271 <212> TYPE: DNA <213> ORGANISM: Homo sapiens<220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION:Incyte ID No: 7476160CB1 <400> SEQUENCE: 65 gtagacagca catctagtactacaagtctt ttgatttggc atcaaatcca acataccttt 60 tattatgctt ttcactttttgctcttctgt tagaagttgt ttcactaaaa atatattata 120 gctccatcat gtattcatctgactaaattc cactgtgcat cttctttctt attgcagctc 180 aaatgatgag acttatgaaagaggttcgag gcagaaatca aacagaagta acagaatttc 240 tcctcttagg actttccgacaatccagatc tacaaggagt cctctttgca ttgtttctgt 300 tgatctatat ggcaaacatggtgggcaatt tggggatgat tgtattgatt aagattgatc 360 tctgtctcca cacccccatgtatttctttc tcagtagcct ctcttttgta gatgcctctt 420 actcttcttc cgtcactcccaagatgctgg tgaacctcat ggctgagaat aaggccattt 480 cttttcatgg atgtgctgcccagttctact tctttggctc cttcctgggg actgagtgct 540 tcctgttggc catgatggcatatgaccgct atgcagccat ttggaacccc ctgctctacc 600 cagttctcgt gtctgggagaatttgctttt tgctaatagc tacctccttc ttagcaggtt 660 gtggaaatgc agccatacatacagggatga cttttaggtt gtccttttgt ggttctaata 720 ggatcaacca tttctactgtgacaccccgc cactgctcaa actctcttgc tctgataccc 780 acttcaatgg cattgtgatcatggcattct caagttttat tgtcatcagc tgtgttatga 840 ttgtcctcat ttcctacctgtgtatcttca ttgccgtctt gaagatgcct tcgttagagg 900 gcaggcacaa agccttctccacctgtgcct cttacctcat ggctgtcacc atattctttg 960 gaacaatcct cttcatgtacttgcgcccta catctagcta ctcaatggag caagacaagg 1020 ttgtctctgt cttttatacagtaataatcc ctgtgctaaa tcccctcatc tatagtttaa 1080 aaaataagga tgtaaaaaaggccctaaaga agatcttatg gaaacacatc ttgtagagcc 1140 atgttaccca tcatttgttacgtagaagaa aatacatttt catgttaact gtattctctg 1200 attgtttaag ctgtttctctgtgttaaagt agataattta aaatgaagta tactttttaa 1260 tatcctagta t 1271 <210>SEQ ID NO 66 <211> LENGTH: 954 <212> TYPE: DNA <213> ORGANISM: Homosapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7476781CB1 <400> SEQUENCE: 66 atgggggacaaccaatcacg ggtcacagaa ttcatcctgg ttggattcca gctcagtgtg 60 gagatggaagtgctcctctt ctggatcttc tccctgttat atctcttcag cctgctgggg 120 aatggggtcatctttgggct catctgcctg gactctaagc ttcacacccc catgtacttc 180 ttcctctcacacctggccgt cattgacatg tcctatgctt ccaacaatgt tcccaagatg 240 ctggcaaacctagtgaacca gaaaagaact atctcgttca tctcttgcat aatgcagact 300 tttttgtatttggcttttgc tgttacagtg tgcctgattt tggtggtgat gtcctatgac 360 agatttgtggccatctgcca tcccctgcat tacactgtca tcatgagctg gagagtgtgc 420 actgtcctggctgtggcttc ctgggtgttc agcttcctcc tggctctggt ccatttagtt 480 ctcattctgaggctgccctt ctgtgggccc caggaggtga accacttctt cggtgaaatc 540 ctgtctgtcctcaagttggc ctgtgctgac acctggctca accaggtggt catctttgca 600 gcctgcatgttcatcctggt agggccgctc tgcctggtgc tggtctccta cttgcacatc 660 ctggcggccatcttgaggat ccagtctggg gagggccgca gaaaggcctt ctctacctgc 720 tcctcccacctctgcgtggt ggggcttttc tttggcagcg ccattgtcat gtacatggcc 780 cccaagtcaagccattctca agaacggagg aagatccttt ccctgtttta cagccttttc 840 aacccgatcctgaaccccct catctacagc cttaggaatg cagaggtgaa aggggctcta 900 aagagagtcctttggaaaca gagatcaatt gaagaatcat ttgagatatc ctga 954 <210> SEQ ID NO 67<211> LENGTH: 1451 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 7487603CB1 <400> SEQUENCE: 67 agttcatata aataaaacat gccagatatgtgaaggaggg ggttatgttt tatatatgtg 60 tgacgttaat ccttctatgc atacgtacaggtgaacataa cataaaaaaa tgttcccggc 120 aaattggaca tctgtaaaag tatttttcttcctgggattt tttcactacc ccaaagttca 180 ggtcatcata tttgcggtgt gcttgctgatgtacctgatc accttgctgg gcaacatttt 240 tctgatctcc atcaccattc tagattcccacctgcacacc cctatgtacc tcttcctcag 300 caatctctcc tttctggaca tctggtactcctcttctgcc ctctctccaa tgctggcaaa 360 ctttgtttca gggagaaaca ctatttcattctcagggtgc gccactcaga tgtacctctc 420 ccttgccatg ggctccactg agtgtgtgctcctgcccatg atggcatatg accggtatgt 480 ggccatctgc aaccccctga gataccctgtcatcatgaat aggagaacct gtgtgcagat 540 tgcagctggc tcctggatga caggctgtctcactgccatg gtggaaatga tgtctgtgct 600 gccactgtct ctctgtggta atagcatcatcaatcatttc acttgtgaaa ttctggccat 660 cttgaaattg gtttgtgtgg acacctccctggtgcagtta atcatgctgg tgatcagtgt 720 acttcttctc cccatgccaa tgctactcatttgtatctct tatgcattta tcctcgccag 780 tatcctgaga atcagctcag tggaaggtcgaagtaaagcc ttttcaacgt gcacagccca 840 cctgatggtg gtagttttgt tctatgggacggctctctcc atgcacctga agccctccgc 900 tgtagattca caggaaatag acaaatttatggctttggtg tatgccggac aaacccccat 960 gttgaatcct atcatctata gtctacggaacaaagaggtg aaagtggcct tgaaaaaatt 1020 gctgattaga aatcatttta atactgccttcatttccatc ctcaaataac aatcacactc 1080 atatagataa tcaacattac ccagaaaactgcataatagt ttacttaaac caaccctgga 1140 aactacttat tttcaataga agtttactattatatcctct attctgattt gtcttataag 1200 taaaactttt catattaaca aatcatttatgaagaataaa ttaagtttcc aagaaagcaa 1260 ttagcattta ttgaatatta gtataacattaaaattagat aattgcctat tatttcatat 1320 ttactttcta tagcatctca gtgtccagctgtgacataag cataataaca ataaatatgc 1380 caaaactgta aaattttgag actagtcaattttgaaataa tttactccaa ataattcaca 1440 atttcccctc a 1451 <210> SEQ ID NO68 <211> LENGTH: 1511 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 58015601CB1 <400> SEQUENCE: 68 ggatataaaa ccatcttgta ttgcagcattttgtcagtgt catctctaat ttcactatgt 60 taataactaa ggattccacc ctataaaagaagcagagtac ctgaattctc ctaaatgaca 120 cgtgtttcca tgcatgtatg tgtatacagtaatacaagat atattatatt acaccttatg 180 ttaatttttt tttatataag aagtattatagctatacttt ttttccgatt actctattgg 240 tagaagagga tttttttaat ttcatgagcataattgagtt ggttccagta acatatttga 300 aaacaaattc aacaaagaat ccattcaaaataatacattt cttaatgctc cctctgaaac 360 actcagcaaa tattgtgcat ctttgacccacagctctgac cttcctgtcc tagatgaggg 420 tttgtctttc tctgccacaa gagcatggaaggcaaccaga catggatcac agacatcacc 480 ctgctgggat tccaggctgg tccagcactggcgattctcc tctgtggact cttctctgtc 540 ttctatacac tcaccctgct ggggaatggggtcatctttg ggattatctg cctggactct 600 aagcttcaca cacccatgta cttcttcctctcacacctgg ccatcattga catgtcctat 660 gcttccaaca atgttcccaa gatgttggcaaacctaatga accagaaaag aaccatctcc 720 tttgttccat gcataatgca gacttttttgtatttggctt ttgctgttac agagtgcctg 780 attttggtgg tgatgtccta tgataggtatgtggccatct gccacccttt ccagtacact 840 gtcatcatga gctggagagt gtgcacgatcctggttctca cgtcctggtc atgtgggttt 900 gccctgtccc tggtacatga aattctccttctaaggttgc ccttctgtgg gccccgggat 960 gtgaaccacc tcttctgtga aattctgtctgtcctcaagc tggcctgtgc tgacacctgg 1020 gttaaccaag tggtcatatt tgctacctgtgtgtttgtct tagtcgggcc tctttccttg 1080 attctggtct cctacatgca catcctcggggccatcctga agatccagac aaaggagggc 1140 cgcataaagg ccttctccac ctgctcctcccacctgtgtg tggttggact attctttggc 1200 atagccatgg tggtttacat ggtcccagactctaatcaac gagaggagca ggagaaaatg 1260 ctgtccctgt ttcacagtgt cttgaacccaatgctgaacc ccctgatcta cagcctgagg 1320 aatgctcagt tgaagggcgc cctccacagagcactccaga ggaagaggtc catgagaacg 1380 gtgtatgggc tttgccttta aaacatgtggtttgctgaag caagaatttt gaatatattt 1440 tgcagaagaa gtttaatata aaaatggtgagtgattgaat tcaagctttg aaaatagggc 1500 aatattcaat g 1511 <210> SEQ ID NO69 <211> LENGTH: 1056 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 6541249CB1 <400> SEQUENCE: 69 atgtctgggg acaacagctc cagcctgaccccaggattct ttatcttgaa tggcgttcct 60 gggctggaag ccacacacat ctggatctccctgccattct gctttatgta catcattgct 120 gtcgtgggga actgtgggct catctgcctcatcagccatg aggaggccct gcaccggccc 180 atgtactact tcctggccct gctctccttcactgatgtca ccttgtgcac caccatggta 240 cctaatatgc tgtgcatatt ctggttcaacctcaaggaga ttgactttaa cgcctgcctg 300 gcccagatgt tttttgtcca tatgctgacagggatggagt ctggggtgct catgctcatg 360 gccctggacc gctatgtggc catctgctaccccttacgct atgccaccat ccttaccaac 420 cctgtcatcg ccaaggctgg tcttgccaccttcttgagga atgtgatgct catcatccca 480 ttcactctcc tcaccaagcg cctgccctattgccggggga acttcatccc ccacacctac 540 tgtgaccata tgtctgtggc caaggtatcctgtggcaatt tcaaggtcaa tgctatttat 600 ggtctgatgg ttgctctcct gattggtgtgtttgatatct gctgtatctc tgtatcttac 660 actatgattt tgcaggctgt tatgagcctgtcatcagcag atgctcgtca caaagccttc 720 agcacctgca catctcacat gtgttccattgtgatcacct atgttgctgc ttttttcact 780 tttttcactc atcgttttgt aggacacaatatcccaaacc acatacacat catcgtggcc 840 aacctttatc tgctactgcc tcctaccatgaacccaattg tttatggagt caagaccaag 900 cagattcagg aaggtgtaat taaatttttacttggagaca agaagaatgt ccaagggttc 960 tgtttttccc aagtcatcag tttagggtctccatttaaaa tggatctaaa tgggaacaat 1020 agactccagg ttcttcgaaa ggagcgggaagaataa 1056 <210> SEQ ID NO 70 <211> LENGTH: 1351 <212> TYPE: DNA <213>ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 7472078CB1 <400> SEQUENCE: 70tgtccaatgt ttgatacaaa aaaaaatgtt tgatatgaaa aaaatcaaac attggacaat 60atgtacatga gtttaaagtc aggaaaaaaa atgaaacctt caaggtagtt cttcttactt 120ctcaaagatg tttagctgta catcttattt atttttttct ctaccctctc atgtgctgga 180ctatgccctc tccatttaca ggtagctcta ctagaaatat ggagagcgga aaccaatcaa 240cagtgactga atttatcttc actggattcc ctcagcttca ggatggtagt ctcctgtact 300tctttccttt acttttcatc tatactttta ttatcattga taacttatta atcttctctg 360ctgtaaggct ggacacccat ctccacaacc ccatgtataa ttttatcagt atattttcct 420ttctggagat ctggtacacc acagccacca ttcccaagat gctctccaac ctcatcagtg 480aaaagaaggc catctcaatg actggctgca tcttgcagat gtatttcttc cactcacttg 540aaaactcaga ggggatcttg ctgaccacca tggccattga cagatacgtt gccatctgca 600accctcttcg ctatcaaatg atcatgaccc cccggctctg tgctcaactc tctgcaggtt 660cctgcctctt cggtttcctt atcctgcttc ccgagattgt gatgatttcc acactgcctt 720tctgtgggcc caaccaaatc catcagatct tctgtgactt ggtccctgtg ctaagcctgg 780cctgtacaga cacgtccatg attctgattg aggatgtgat tcatgctgtg accatcatca 840ttaccttcct aatcattgcc ctgtcctatg taagaattgt cactgtgata ttgaggattt 900cctcttctga agggaggcaa aaggcttttt ctacctgtgc aggccacctc atggtcttcc 960tgatattctt tggcagtgta tcactcatgt acttgcgttt cagcgacact tatccaccag 1020ttttggacac agccattgca ctgatgttta ctgtacttgc tccattcttc aatcccatca 1080tttatagcct gagaaacaag gacatgaaca atgcgattaa aaaactgttc tgtcttcaaa 1140aagtgttgaa caagcctgga ggttaataca gagccacagg ttcccttccg ttgcttttgt 1200tttgttttgt tttttgagat ggagtttcac tcttgttgcc tgggctggag tgcaatggca 1260tgatcttggc tcactgcaac ctccacctcc tggttttgaa caattctcct gcctcagcct 1320ccctagtagc cgcgattaca ggcatgcacc a 1351 <210> SEQ ID NO 71 <211> LENGTH:1201 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7472087CB1<400> SEQUENCE: 71 tatagtatac gaatgaaccc cttatcctca caaaactgagttttaaccaa aagcatgact 60 gcttttcatt tatatggttt cagatccggc taacgagctcatatctccct cattatgtct 120 gttctcaata actccgaagt caagcttttc cttctgattgggatcccagg actggaacat 180 gcccacattt ggttctccat ccccatttgc ctcatgtacctgcttgccat catgggcaac 240 tgcaccattc tctttattat aaagacagag ccctcgcttcatgagcccat gtattatttc 300 cttgccatgt tggctgtctc tgacatgggc ctgtccctctcctcccttcc taccatgttg 360 agggtcttct tgttcaatgc catgggaatt tcacctaatgcctgctttgc tcaagaattc 420 ttcattcatg gattcactgt catggaatcc tcagtacttctaattatgtc tttggaccgc 480 tttcttgcca ttcacaatcc cttaagatac agttctatcctcactagcaa cagggttgct 540 aaaatgggac ttattttagc cattaggagc attctcttagtgattccatt tcccttcacc 600 ttaaggagat taaaatattg tcaaaagaat cttctttctcactcatactg tcttcatcag 660 gataccatga agctggcctg ctctgacaac aagaccaatgtcatctatgg cttcttcatt 720 gctctctgta ctatgctgga cttggcactg attgttttgtcttatgtgct gatcttgaag 780 actatactca gcattgcatc tttggcagag aggcttaaggccctaaatac ctgtgtctcc 840 cacatctgtg ctgtgctcac cttctatgtg cccatcatcaccctggctgc catgcatcac 900 tttgccaagc acaaaagccc tcttgttgtg atccttattgcagatatgtt cttgttggtg 960 ccgcccctta tgaaccccat tgtgtactgt gtaaagactcgacaaatctg ggagaagatc 1020 ttggggaagt tgcttaatgt atgtgggaga taagaacttgaacaattagg taataaatta 1080 tcaaccagta ggcatttact gtcatttgct atgtgcttaatgccatagaa gtcactaatg 1140 aaggactgga tgatggaagt gaaaagctat gtagtgcagaatttataata aagttgagaa 1200 t 1201 <210> SEQ ID NO 72 <211> LENGTH: 1251<212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7472089CB1<400> SEQUENCE: 72 tttgaaaatt agaaataata actcagtgaa tcttgaagtgccagagagat gttacaagtg 60 ataaactatg tattatgtgt tatgttaaat gactgaaacatccctgtctt ctcagtgctt 120 ccctatgtcg gtcctcaata ataccattgc tgagcctctgatcttcctcc tgatgggcat 180 tccaggcctg aaagccaccc agtactggat ctccatccctttttgtctcc tatatgttgt 240 tgccgtctct ggaaatagca tgatcctgtt tgtggtcctctgtgaacgga gcctccataa 300 gcctatgtac tatttcctct ctatgctttc agccacagacctgagcttgt ccctgtgtac 360 actttctact acccttggtg tcttctggtt tgaagcccgagaaatcaacc taaatgcctg 420 cattgcccag atgttctttc tacacggatt tactttcatggagtctgggg ttctactggc 480 catggccttt gatcgttttg tggccatctg ttacccactgagatacacta ccatccttac 540 caatgcccga attgccaaga ttgggatgag catgttgataagaaatgttg ccgtcatgtt 600 gccagtcatg ctctttgtca agaggttgtc cttctgcagttctatggtcc tttcacattc 660 ttactgctac catgttgatc tcatccaact ctcctgcacagacaatagga tcaacagcat 720 ccttggtctg tttgcgcttt tgtccactac agggtttgactgcccttgca tcctgctctc 780 ctatatcctg atcattcgat ctgtcctcag cattgcttcctcagaagaga ggcggaaagc 840 cttcaacacc tgcacatccc acatcagtgc tgtttccatcttctacctcc ctctcatcag 900 tttgtctctt gtccatcgct atggccattc agcacctccatttgtccaca tcatcatggc 960 caatgtcttt ctgctaatcc ctcctgtgct caaccctattatttacagtg taaagattaa 1020 gcagattcaa aaggccatta tcaaggtctt aattcagaagcactccaaat ctaatcatca 1080 gctatttctg attagagata aagccattta tgaataagtgctttgctaca atggagtaat 1140 tgtcccaaag tgcccacaca tgcctccaac agtccaaactaagcaattta taggttatgt 1200 gacatttatt tagtcaattt ctttgtcaat aaattcatgtcattgccaac t 1251 <210> SEQ ID NO 73 <211> LENGTH: 1221 <212> TYPE: DNA<213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature<223> OTHER INFORMATION: Incyte ID No: 7474902CB1 <400> SEQUENCE: 73tctttaattt ccaccaggtg caatcaccag tactgcctca atttacttca ggattttgga 60gggcacccac cttccccctt gtctcctcac acaatgaccc tgggatccct gggaaacagc 120agcagcagcg tttctgctac cttcctgctg agtggcatcc ctgggctgga gcgcatgcac 180atctggatct ccatcccact gtgcttcatg tatctggttt ccatcccggg caactgcaca 240attcttttta tcattaaaac agagcgctca cttcatgaac ctatgtatct cttcctgtcc 300atgctggctc tgattgacct gggtctctcc ctttgcactc tccctacagt cctgggcatc 360ttttgggttg gagcacgaga aattagccat gatgcctgct ttgctcagct ctttttcatt 420cactgcttct ccttcctcga gtcctctgtg ctactgtcta tggcctttga ccgctttgtg 480gctatctgcc accccttgca ctatgtttcc attctcacca acacagtcat tggcaggatt 540ggcctggtct ctctgggtcg tagtgtagca ctcatttttc cattaccttt tatgctcaaa 600agattcccct attgtggctc cccagttctc tcacattctt attgtctcca ccaagaagtg 660atgaaattgg cctgtgccga catgaaggcc aacagcatct acggcatgtt tgtcatcgtc 720tctacagtgg gtatagactc actgctcatc ctcttctctt atgctctgat cctgcgcacc 780gtgctgtcca tcgcctccag ggctgagaga ttcaaggccc ttaacacctg tgtttcccac 840atctgtgctg tgctgctctt ctacactccc atgattggcc tctctgtcat ccatcgcttt 900ggaaagcagg caccccacct ggtccaggtg gtcatgggtt tcatgtatct tctctttcct 960cctgtgatga atcccattgt ctacagtgtg aagaccaaac agatccggga tcgagtgacg 1020catgcctttt gttactaact gtgtctagtg ttagagccac tgtctcctga aacgtgccct 1080tgtttgccta tcctttataa tttctaacat gcataaaata aaggagacat ttacttactc 1140aacaaacatg tacagggatg agttacagtc cttacagaac cctcactctg ttgtggccag 1200ggcagggggg ggtaaaatgt a 1221 <210> SEQ ID NO 74 <211> LENGTH: 1276 <212>TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY:misc_feature <223> OTHER INFORMATION: Incyte ID No: 7475057CB1 <400>SEQUENCE: 74 cctcactacc ccttcctccc actacaatac atatagactt ttaggagcaaaggattctcc 60 tatcttagct agaattgcga ccttaattat ccatccaaac ccccctaaccaaaagttata 120 aacctgtgat cctcccagcc ctgcactact cctacacgta tgccatggatgggtttgtgc 180 cactgtgaga cccccaaaat ctctcccctt atcttccctg tcaggagtcatgcccccatg 240 agccctcaag ttgtgcccac cacagaatgg cagaaactct acaactcaattccaccttcc 300 tacacccaaa cttcttcata ctgactggct ttccagggct aggaagtgcccagacttggc 360 tgacactggt ctttgggccc atttatctgc tggccctgct gggcaatggagcactgccgg 420 cagtggtgtg gatagactcc acactgcacc agcccatgtt tctactgttggccatcctgg 480 cagccacaga cctgggctta gccacatcta tagccccagg gttgctggctgtgctgtggc 540 ttgggccccg atctgtgcca tatgctgtgt gcctggtcca gatgttctttgtacatgcac 600 tgactgccat ggaatcaggt gtgcttttgg ccatggcctg tgatcgtgctgcggcaatag 660 ggcgtccact gcactaccct gtcctggtca ccaaagcctg tgtgggttatgcagccttgg 720 ccctggcact gaaagctgtg gctattgttg tacctttccc actgctggtggcaaagtttg 780 agcacttcca agccaagacc ataggccata cctattgtgc acacatggcagtggtagaac 840 tggtggtggg taacacacag gccaccaact tatatggtct ggcactttcactggccatct 900 caggtatgga tattctgggt atcactggct cctatggact cattgcccatgctgtgctgc 960 agctacctac ccgggaggcc catgccaagg cctttggtac atgtagttctcacatctgtg 1020 tcattctggc cttctacata cctggtctct tctcctacct cacacaccgctttggtcatc 1080 acactgtccc aaagcctgtg cacatccttc tctccaacat ctacttgctgctgccacctg 1140 ccctcaaccc cctcatctat ggggcccgca ccaagcagat cagagaccgactcctggaaa 1200 ccttcacatt cagaaaaagc ccgttgtaat gtccagtggt aacaatggagcctaagagtg 1260 gaggtgaggg gacaat 1276 <210> SEQ ID NO 75 <211> LENGTH:1509 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7475261CB1<400> SEQUENCE: 75 gcctggggca gtcagggctc atcccctgga ggacaccggacaccctgtgg atgcccttca 60 tggttattgg gtcccttgga gaagtccagg tggtgaaaaataggacacag ctttgagaga 120 tgagggagac tggtggtgac aggctcagga gggcattccagacccagtgt tacaggctga 180 gacctagaat ctatatcatc agaggttagt gcttaacatgtatctgggtg gggagctgct 240 tttgctcccc actggtgctc tggggagcca cgtggcctctctttacacca aaactcccta 300 tccaggtcca gctccactct ccctctgccc cagcttccctgcagcccttt cctcttgctc 360 tttgatgttt tgtaggcctg cagctcccaa gcacagaggcatgagtgggg agaatgtcac 420 cagggtcggc accttcatcc tggtgggctt ccccacggccccagggctgc agtacctgct 480 cttcctcctc ttcctgctca cctacctctt tgtcctggtggagaacctgg ccatcatcct 540 caccgtctgg agcagcacct ccctccacag gcccatgtactactttctga gctccatgtc 600 tttcctagag atctggtacg tgtctgacat cacccccaagatgctggagg gcttcctcct 660 ccagcagaaa cgcatctctt tcgtcgggtg catgacgcagctctacttct tcagctccct 720 ggtgtgcacc gagtgtgtgc ttctggcctc catggcctacgaccgctacg tggccatctg 780 ccacccgctg cgctaccacg tccttgtgac cccggggctgtgcctccagc tggtgggctt 840 ctcctttgtg agtggcttca ccatctccat gatcaaggtctgttttatct ccagcgtcac 900 gttctgtggc tccaacgtct tgaaccactt cttctgtgacatttccccca tcctcaagct 960 ggcctgcacg gacttctcca ctgcagagct ggtggatttcattctggcct tcatcatcct 1020 ggtgtttcca ctcctggcca ccatgctgtc atatgcgcacatcaccctgg ctgtcctgcg 1080 catcccctcg gccaccggct gctggagagc cttcttcacctgcgcctctc acctcaccgt 1140 ggtcaccgtc ttctatacag ccttgctttt catgtatgtccggccccagg ccattgattc 1200 ccggagctcc aacaagctca tctctgtttt gtacacagttatcaccccca tcttgaaccc 1260 cttgatatac tgcctgagga ataaggaatt taagaatgccttgaaaaaag ccttcggctt 1320 gacgagctgc gccgtagagg ggaggctttc tagtcttctggaacttcatc tccaaataca 1380 cagccagcct ctctgaggag gccatttgac tgtttgcattattgtagtac cgcatttatt 1440 taaaaattac ttccaaatct atttttctcc ttcaggaaaaaaactgaggt tgaggttaat 1500 agcataggt 1509 <210> SEQ ID NO 76 <211>LENGTH: 1301 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE:<221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:7475262CB1 <400> SEQUENCE: 76 actatgaata tatacttggt gagtgactgtttcattactt agaattttta agatccccaa 60 gaccaattgt agatatttct cttatattttccattgctgc ttaagtaatg cttaccaact 120 aaccaaccaa ccaaggagaa aagatcctctctatgacaga gtttcatctg caaagccaaa 180 tgccctcaat aagactcatc ttcagaaggctgtccttagg cagaattaaa cccagtcaga 240 gccccaggtg ttcaacctca tttatggtggtgccttcttt ctccatcgca gagcactgga 300 gaaggatgaa aggggcaaac ctgagccaagggatggagtt tgagctcttg ggcctcacca 360 ctgaccccca gctccagagg ctgctcttcgtggtgttcct gggcatgtac acagccactc 420 tgctggggaa cctggtcatg ttcctcctgatccatgtgag tgccaccctg cacacaccca 480 tgtactccct cctgaagagc ctctccttcttggatttctg ctactcctcc acggttgtgc 540 cccagaccct ggtgaacttc ttggccaagaggaaagtgat ctcttatttt ggctgcatga 600 ctcagatgtt cttctatgcg ggttttgccaccagtgagtg ctatctcatc gctgccatgg 660 cctatgaccg ctatgccgct atttgtaaccccctgctcta ctcaaccatc atgtctcctg 720 aggtctgtgc ctcgctgatt gtgggctcctacagtgcagg attcctcaat tctcttatcc 780 acactggctg tatctttagt ctgaaattctgcggtgctca tgtcgtcact cacttcttct 840 gtgatgggcc acccatcctg tccttgtcttgtgtagacac ctcactgtgt gagatcctgc 900 tcttcatttt tgctggtttc aaccttttgagctgcaccct caccatcttg atctcctact 960 tcttaattct caacaccatc ctgaaaatgagctcggccca gggcaggttt aaggcatttt 1020 ccacctgtgc atcccacctc actgccatctgcctcttctt tggcacaaca ctttttatgt 1080 acctgcgccc caggtccagc tactccttgacccaggaccg cacagttgct gtcatctaca 1140 cagtggtgat cccagtgctg aaccccctcatgtactcttt gagaaacaag gatgtgaaga 1200 aagctttaat aaaggtttgg ggtaggaaaacaatggaatg atttctcaat gcattaccac 1260 atatctttag aaagtcaagg gaacttttaccttaggtggt g 1301 <210> SEQ ID NO 77 <211> LENGTH: 1051 <212> TYPE: DNA<213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature<223> OTHER INFORMATION: Incyte ID No: 7475266CB1 <400> SEQUENCE: 77gaagagcagt gagggtccat gttaaggtaa ttcatacttt ctattttcac agaaatgcct 60aaagaagaat gaccatggaa aattattcta tggcagctca gtttgtctta gatggtttaa 120cacagcaagc agagctccag ctgcccctct tcctcctgtt cctgggaatc tatgtggtca 180cagtagtggg caacctgggc atgattctcc tgattgcagt cagccctcta cttcacaccc 240ccatgtacta tttcctcagc agcttgtcct tcgtcgattt ctgctattcc tctgtcatta 300ctcccaaaat gctggtgaac ttcctaggaa agaagaatac aatcctttac tctgagtgca 360tggtccagct cgttttcttt gtggtctttg tggtggctga gggttacctc ctgactgcca 420tggcatatga tcgctatgtt gccatctgta gcccactgct ttataatgcg atcatgtcct 480catgggtctg ctcactgcta gtgctggctg ccttcttctt gggctttctc tctgccttga 540ctcatacaag tgccatgatg aaactgtcct tttgcaaatc ccacattatc aaccattact 600tctgtgatgt tcttcccctc ctcaatctct cctgctccaa cacacacctc aatgagcttc 660tactttttat cattgcgggg tttaacacct tggtgcccac cctagctgtt gctgtctcct 720atgccttcat cctctacagc atccttcaca tccgctcctc agagggccgg tccaaagctt 780ttggaacatg cagctctcat ctcatggctg tggtgatctt ctttgggtcc attaccttca 840tgtatttcaa gcccccttca agtaactccc tggaccagga gaaggtgtcc tctgtgttct 900acaccacggt gatccccatg ctgaaccctt taatatacag tctgaggaat aaggatgtga 960agaaagcatt aaggaaggtc ttagtaggaa aatgagtcct gatttggggg atttatagat 1020gggaaaaatg aatagttcca atgaacatat a 1051 <210> SEQ ID NO 78 <211> LENGTH:1490 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7475284CB1<400> SEQUENCE: 78 gggtggtgag ggaagaaaaa ttacttattg ggtgcgatgtacaccatttg ggtgatgagt 60 atgctataaa cccaggcttc agtacttggc aatatatccatgtaacaaaa tatatccatg 120 taacaaaaat gcacttgtgc ctcttaaatc tgtaaaaatgaaaagttaca aacaagaaaa 180 gaaaccactg cagaatccag tacagagcaa agcaggcagatcaagatgat tctaccagga 240 agcattcctc tgtaactatc tagatctctt tcttcttttccatttcattc atctaaacac 300 aggtaattta catgcatatt aaatttaacc acttatttcttttcacagac acccaagagt 360 tgattcctcc ccaggaatga gaaatcacac aatggtgactgaattcatcc ttctgggaat 420 ccctgagaca gagggcctag agacagccct tttattcctgttctcctcat tttatttatg 480 caccctcttg ggaaacgtgc ttatccttac agctatcatctcctccactc gacttcacac 540 tcctatgtat tttttcttgg gaaacctctc catctttgacctgggtttct cttcaacgac 600 tgttcccaag atgttgttct acctttcggg gaacagccatgctatctcat atgcaggctg 660 cgtgtcccag cttttcttct accatttcct aggctgtactgagtgtttcc tctacacagt 720 gatggcctgt gaccgctttg ttgccatatg ttttcctttgagatacacgg tcatcatgaa 780 ccacagggtg tgctttatgt tggccacggg gacctggatgattggctgtg tccatgccat 840 gatcctaact cccctcacct tccagttacc ttactgtggccctaacaagg tgggctatta 900 cttctgtgat attcctgcag tgttacctct agcctgtaaggacacatcct tagcccagag 960 ggtaggtttt acaaatgttg gtcttttgtc tctcatttgcttttttctca tccttgtttc 1020 ctatacttgc attgggattt ccatatcaaa aatccgctcagcagagggca ggcagcgggc 1080 cttctccacc tgcagcgctc acctcactgc aatcctttgtgcttatgggc cagtcatcgt 1140 tatctatcta caacccaatc ccagtgcctt gcttggttccataattcaga tattgaataa 1200 tctggtaacc ccaatgttga atccactaat ctatagccttaggaataagg atgtaaaatc 1260 agatcagccc tgaggaatgt atttcccaag aaaagctttgctctgggaaa taaatgagaa 1320 catttaaagc tttgctggat ttaagatttt gattacattttgaagtttga ctctccactc 1380 cctgagaaaa tttcccatct gctgctgcca aggcaagttgaaacgaaatg tactccaaat 1440 caatctacta cttaacctcg ctcttttaaa atatctgtctgttggtgtat 1490 <210> SEQ ID NO 79 <211> LENGTH: 1288 <212> TYPE: DNA<213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature<223> OTHER INFORMATION: Incyte ID No: 7475309CB1 <400> SEQUENCE: 79catatatcac aatgttctta aatcttgctt tagttaccct caacaactct gaacatttat 60ttgtgtagaa tttggattaa atggggcaaa gagatattat ttctaatgtt tctttttctc 120cctgagtgaa gatcctgaat ctgaagacac attcatcagt catgtcccag gtgactaaca 180ccacacaaga aggcatctac ttcatcctca cggacatccc tggatttgag gcctcccaca 240tctggatctc catccccgtc tgctgtctct acaccatctc catcatgggc aataccacca 300tcctcactgt cattcgcaca gagccatctg tccaccagcg catgtatctg tttctctcca 360tgctggccct gacggacctg ggtctcaccc tcaccaccct acccacagtc atgcagcttc 420tctggttcaa cgttcgtaga atcagctctg aggcctgttt tgctcagttt ttcttccttc 480atggattctc ctttatggag tcttctgtcc tcctggctat gtccgttgac tgctatgtgg 540ccatctgctg tcccctccat tatgcctcca tcctcaccaa tgaagtcatt ggtagaactg 600ggttagccat catttgctgc tgtgttctgg cggttcttcc ctcccttttc ttactcaagc 660gactgccttt ctgccactcc caccttctct ctcgctccta ttgcctccac caggatatga 720tccgcctggt ctgtgctgac atcaggctca acagctggta tggatttgct cttgccttgc 780tcattattat cgtggatcct ctgctcattg tgatctccta tacacttatt ctgaaaaata 840tcttgggcac agccacctgg gctgagcgac tccgtgccct caataactgc ctgtcccaca 900ttctagctgt cctggtcctc tacattccca tggttggtgt atctatgact catcgctttg 960ccaagcatgc ctctccactg gtccatgtta tcatggccaa tatctacctg ctggcacccc 1020cggtgatgaa ccccatcatt tacagtgtaa agaacaagca gatccaatgg ggaatgttaa 1080atttcctttc cctcaaaaat atgcattcaa gatgagggaa tgcatttctt aaattactga 1140caagtatgag tcataggctt aaggggggaa tatattcaga attaggaaac tataaaataa 1200aacttcatca taatattaag gcagtatgac aagtccctgg cttttagcat ggaatttttg 1260gctgaggtga gctagcagca gtgattct 1288 <210> SEQ ID NO 80 <211> LENGTH:1124 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7477359CB1<400> SEQUENCE: 80 ctccatgatc ctctcagctc atgtgttctg ttattctaaatttaattgtt ttggatgtac 60 ccattccatt cctgccttag gtgcggatcc ccctggagggatgggattgg gcaatgagag 120 ttccctaatg gatttcatcc ttctaggctt ctcagaccaccctcgtctgg aggctgttct 180 ctttgtattt gtccttttct tctacctcct gacccttgtgggaaacttca ccataatcat 240 catctcatat ctggatcccc ctcttcatac cccaatgtacttttttctca gcaacctctc 300 tttactggac atctgcttca ctactagcct tgctcctcagaccttagtta acttgcaaag 360 accaaagaag acgatcactt acggtggttg tgtggcgcaactctatattt ctctggcact 420 gggctccact gaatgtatcc tcttggctga catggccttggatcggtaca ttgctgtctg 480 caaacccctc cactatgtag tcatcatgaa cccacggctttgccaacagc tggcatctat 540 ctcctggctc agtggtttgg ctagttccct aatccatgcaacttttacct tgcaattgcc 600 tctctgtggc aaccataggc tggaccattt tatttgcgaagtaccagctc ttctcaagtt 660 ggcttgtgtg gacaccactg tcaatgaatt ggtgctttttgttgttagtg ttctgtttgt 720 tgtcattcca ccagcactca tctccatctc ctatggcttcataactcaag ctgtgctgag 780 gatcaaatca gtagaggcaa ggcacaaagc cttcagcacctgctcctccc accttacagt 840 ggtgattata ttctatggca ccataatcta cgtgtacctgcaacctagtg acagctatgc 900 ccaggaccaa gggaagttta tctccctctt ctacaccatggtgaccccca ctttaaatcc 960 tatcatctat actttaagga acaaggatat gaaagaggctctgaggaaac ttctctcggg 1020 aaaattgtga ttcctatgga catgatttgc aaggaattcattataagcca ggtagcttat 1080 tcagcttcta tttagtcaaa ctcatagttc taaatttcacatgt 1124 <210> SEQ ID NO 81 <211> LENGTH: 1447 <212> TYPE: DNA <213>ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 58004547CB1 <400> SEQUENCE: 81gcctgcagct cccaagcaca gaggcatgag tggggagaat gtcaccaagg tcagcacctt 60catcctggtg ggcctcccca cggccccagg gctgcagtac ctgctcttcc tcctcttcct 120gctcacctac ctctttgtcc tggtggagaa cctggccatc atcctcatcg tctggagcag 180cacctccctc cacaggccca tgtactactt tctgagctcc atgtctttcc tggagatctg 240gtacgtgtct gacatcaccc ccaagatgct ggagggcttc ctcctccagc agaaacgcat 300ctctttcgtc gggtgcatga cgcagctcta cttcttcagc tccctggtgt gcaccgagtg 360tgtgcttctg gcctccatgg cctacgaccg ctacgtggcc atctgccacc cgctgcgcta 420ccacgtcctt gtgaccccgg ggctgtgcct ccagctggtg ggcttctcct ttgtgagtgg 480cttcaccatc tccatgatca aggtctgttt tatctccagc gtcacgttct gtggctccaa 540cgtcttgaac cacttcttct gtgacatttc ccccatcctc aagctggcct gcacggactt 600ctccactgca gagctggtgg atttcatcct ggccttcatc atcctggtgt ttccactcct 660ggccaccata ctgtcatatt ggcacatcac cctggctgtc ctgcgcatcc cctcggccac 720cggctgctgg agagccttct ctacctgcgc ctctcacctc accgtggtca ccgtcttcta 780tacagccttg cttttcatgt atgtccggcc ccaagccatt gattcccaga gctccaacaa 840gctcatctct gccgtgtaca ctgttgtcac gccaataatt aaccctttga tttactgcct 900gaggaacaag gaatttaagg acgccttgaa aaaggccttg ggcttgggtc aaacttcaca 960ctaagacaac taaatgtcct agagtaaaat ctgtagtgat gaaacaacat tgtatgtggc 1020actttgtgct ctttaaatta atttttaagt taaatttaac aaacctacag aactaagtga 1080aatttaacaa acctacacaa ctgtgcacaa gtaacaagcc ttcgtctgca tatgttttca 1140caaaaggact gtgctcatgg aaccagctcc cagatcaaga actagaagct gccttcacgc 1200cctctcccag tcattaaccc ttctccacaa aaagcactgt cctgacttcc aaaaccagat 1260gctagcattg gtgtttctga ggggcttaca cataaagtat gtgccctgtt atgttcagct 1320tctttcattc accgtgttgc ttgagtgaat ccttgatgtt tttgcatgta acaataattc 1380atgcattctc attgctatcc aatattcata ataaataata catttatact gtataataaa 1440aaaaaaa 1447 <210> SEQ ID NO 82 <211> LENGTH: 1026 <212> TYPE: DNA <213>ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 7476156CB1 <400> SEQUENCE: 82tgattgctcg tctttagttt gaatattttc agtgacaggg aatttactac atccatcaaa 60aaactaaatc caggcacaca tacacttgaa gcaatggata aagaaaacag ctcaatggtg 120actgagttta tcttcatggg catcacccag gaccctcaga tggagatcat cttcttcgtg 180gtcttcctca tagtttacct ggttaatgta gtggggaata ttggtatgat tatcctgatt 240acaacagaca ctcagcttca cacacccatg tattttttcc tctgcaacct ctcctttgtt 300gacctgggct actcctcagc cattgccccc aggatgctgg ctgacttcct aacaaatcac 360aaagttatct ccttctccag ctgtgccacc cagtttgctt tttttgtagg ttttgtggat 420gctgagtgct atgtcctggc agccatggcc tatggtcgtt ttgtggccat ttgtcgaccc 480ctccactata gcaccttcat gtccaagcag gtctgcttgg ctctcatgct gggctcttac 540ctggctggtc tagtgagttt agtagcccac actaccctca ccttcagcct gagttactgt 600ggttccaata tcatcaatca tttcttctgc gaaatcccac cactcttggc cctctcttgc 660tcagacacct acatcagtga gatcttgctc ttcagtctgt gtggcttcat tgaattcagc 720accatcctca tcatcttcat ctcctatacc tttatccttg ttgcaatcat cagaatgcgt 780tcagctgaag gccgccttaa ggctttctcc acctgcgggt ctcaccttac tggcatcacc 840ctcttctatg gcacagtcat gtttatgtac ctgaggccaa catccagcta ctccctggac 900caagacaagt gggcctctgt gttctacacg gttatcatcc ccatgttaaa tcccttgatc 960tacagtttgc ggaacaagga tgtgaaagct gctttcaaaa agctaattgg aaaaaaatct 1020caataa 1026 <210> SEQ ID NO 83 <211> LENGTH: 1481 <212> TYPE: DNA <213>ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 7475114CB1 <400> SEQUENCE: 83gactcttgct agtctgtata gactaatttt ttaatttttt tctcctttat tctttttttg 60catattttct caccttgaca ggcactgaag agaatctagt atggccaatg tcaccttggt 120gacaggattt cttcttatgg ggttttctaa tatccagaag ctgcggattt tatatggtgt 180gctcttccta ctgatttacc tggcagccct aatgagtaac cttctcatca ttactctcat 240taccctggac gtaaagctcc aaacacccat gtacttcttc ctgaagaact tatccttttt 300ggatgtcttc ctggtgtctg ttccaatccc aaaattcatt gtcaacaacc taacccacaa 360caattccatt tccattctag gatgtgcctt ccagctactt ttaatgactt ccttctcagc 420aggagagata tttatcctca ctgccatgtc ctatgaccgc tatgtagcca tctgctgtcc 480cctgaactac gaggtaatca tgaatactgg agtctgtgtg ttaatggcaa gtgtttcctg 540ggccattgga gggctctttg gtactgcgta cacagctggc acattttcca tgcctttctg 600tggctccagt gtgattccac agtttttctg tgatgttcct tcattactaa ggatttcctg 660ttctgaaaca ctaatggtaa tttatgcagg tattggagtt ggtgcatgtt taagcatttc 720ttgtttcatc tgtattgtga tctcttacat ttatatcttc tccactgtac tgaagatccc 780taccactaaa ggtcagtcca aagctttttc cacatgcttc ccccatctca ctgttttcac 840tgtttttatc ataactgctt attttgttta tcttaagcca ccttcaaatt caccatctgt 900tattgacagg ctgctttctg tgatctacac tgtgatgcct ccagtattta accctgtaac 960ctacagcctg cggaacaatg acatgaaatg tgctctgata aggttgctgc agaaaacata 1020tggtcaggag gcttacttca tttaacactt tcaagttctg tcagtgatac agtgccttac 1080agatcacaag aaactttcct tatttgtaac tttggaaaga cctgagaaaa gaaagcaata 1140tactcaaatt attttttccc tgaagaaata aatactcaag agcctaactg actatttcta 1200agtcacttaa ttgcattaca tcaggataat acatagtgtt atagtaatca tttggtattc 1260ttctatgaca aagcatttct gcctttgtat tataactttc tgaaagaatt ggttctgttt 1320aacatgatgc tttcatcttt ggtctcttaa taacccattt tctctatttt attcactgag 1380aacaaattaa aaatgctgag gtgattcaat gagtgcagta taatgcattt gcattatact 1440acccagataa aattcacatg actcccctga gaatctagct a 1481 <210> SEQ ID NO 84<211> LENGTH: 1106 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 55003505CB1 <400> SEQUENCE: 84 ccacatagag aatggattct catttctcaattaagtgcta aatgctgggt gctctttata 60 tccccagagg gagagagacc aagggtgagaagaaatgtcc aacgccagcc tcgtgacagc 120 attcatcctc acaggccttc cccatgccccagggctggac gccctcctct ttggaatctt 180 cctggtggtt tacgtgctca ctgtgctggggaacctcctc atcctgctgg tgatcagggt 240 ggattctcac ctccacaccc ccatgtactacttcctcacc aacctgtcct tcattgacat 300 gtggttctcc actgtcacgg tgcccaaaatgctgatgacc ttggtgtccc caagcggcag 360 ggctatctcc ttccacagct gcgtggctcagctctatttt ttccacttcc tggggagcac 420 cgagtgtttc ctctacacag tcatgtcctatgatcgctac ttggccatca gttacccgct 480 caggtacacc agcatgatga gtgggagcaggtgtgccctc ctggccaccg gcacttggct 540 cagtggctct ctgcactctg ctgtccagaccatattgact ttccatttgc cctactgtgg 600 acccaaccag atccagcact acttctgtgacgcaccgccc atcctgaaac tggcctgtgc 660 agacacctca gccaacgtga tggtcatctttgtggacatt gggatagtgg cctcaggctg 720 ctttgtcctg atagtgctgt cctatgtgtccatcgtctgt tccatcctgc ggatccgcac 780 ctcagatggg aggcgcagag cctttcagacctgtgcctcc cactgtattg tggtcctttg 840 cttctttgtt ccctgtgttg tcatttatctgaggccaggc tccatggatg ccatggatgg 900 agttgtggcc attttctaca ctgtgctgacgccccttctc aaccctgttg tgtacaccct 960 gagaaacaag gaggtgaaga aagctgtgttgaaacttaga gacaaagtag cacatcctca 1020 gaggaaataa atactaggaa gtaaatacactagtttgttt aaaaatagta atctaattta 1080 gttattcatg tgaaattgat tatatg 1106<210> SEQ ID NO 85 <211> LENGTH: 1601 <212> TYPE: DNA <213> ORGANISM:Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7474916CB1 <400> SEQUENCE: 85 gtaggacatacctaaggttc agtgaggttt gagagagagc atcagagaga aggtaggatg 60 gcctaaagaaagaacattta gtaagtggta ctacactagg tgaatatata aaaaataaca 120 agggacattttttttactgg caaaaatatt tcattctctg ggtcttcatg cagatatatt 180 caagcaatggaagggaaaaa tcaaaccaat atctctgaat ttctcctcct gggcttctca 240 agttggcaacaacagcaggt gctactcttt gcacttttcc tgtgtctcta tttaacaggg 300 ctgtttggaaacttactcat cttgctggcc attggctcgg atcactgcct tcacacaccc 360 atgtatttcttccttgccaa tctgtccttg gtagacctct gccttccctc agccacagtc 420 cccaagatgctactgaacat ccaaacccaa acccaaacca tctcctatcc cggctgcctg 480 gctcagatgtatttctgtat gatgtttgcc aatatggaca attttcttct cacagtgatg 540 gcatatgaccgttacgtggc catctgtcac cctttacatt actccaccat tatggccctg 600 cgcctctgtgcctctctggt agctgcacct tgggtcattg ccattttgaa ccctctcttg 660 cacactcttatgatggccca tctgcacttc tgctctgata atgttatcca ccatttcttc 720 tgtgatatcaactctctcct ccctctgtcc tgttccgaca ccagtcttaa tcagttgagt 780 gttctggctacggtggggct gatctttgtg gtaccttcag tgtgtatcct ggtatcctat 840 atcctcattgtttctgctgt gatgaaagtc ccttctgccc aaggaaaact caaggctttc 900 tctacctgtggatctcacct tgccttggtc attcttttct atggagcaaa cacaggggtc 960 tatatgagccccttatccaa tcactctact gaaaaagact cagccgcatc agtcattttt 1020 atggttgtagcacctgtgtt gaatccattc atttacagtt taagaaacaa tgaactgaag 1080 gggactttaaaaaagaccct aagccggccg ggcgcggtgg ctcacgcctg taatcccagc 1140 actttgggaggccgaggcgg gtggatcatg aggtcaggag atcgagacca tcctggctaa 1200 caaggtgaaaccccgtctct actaaaaata caaaaaatta gccgggcgcg gtggcgggcg 1260 cctgtagtcccagctactcg ggaggctgag gcaggagaat ggcgtgaacc cgggaagcgg 1320 agcttgcagtgagccgagat tgcgccactg cagtccgcag tccggcctgg gcgacagagc 1380 gagactccgtctcaaaaaaa aaaaaaaaaa aaaaaaaaac cctaagccaa agaaaaatct 1440 tctcccactgatttatacag gctgcaggga gttcaacagg agtcatattt taatatcatt 1500 ttcattctcatcataatggc aaagctgtta ttaaatatct aattagactt attactaacc 1560 taagtttactacaaactcta ggagtaacat aatcttatta t 1601 <210> SEQ ID NO 86 <211> LENGTH:1327 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7472365CB1<400> SEQUENCE: 86 acttacctaa agtgctctgt atacagtatg tttcaaagtgatagaatttc ctgcaaaaaa 60 tcatgtgcac aaatgtatgt ttcttatatt aaatttttgtctccgaactg cagaagcctg 120 tgtggttaca tgcagattgg gtgagcatac atttctgtagactgtggact tatgcattca 180 caagcaggat gttccttccc aatgacaccc agtttcacccctcctccttc ctgttgctgg 240 ggatcccagg actagaaaca cttcacatct ggatcggctttcccttctgt gctgtgtaca 300 tgatcgcact catagggaac ttcactattc tacttgtgatcaagactgac agcagcctac 360 accagcccat gttctacttc ctggccatgt tggccaccactgatgtgggt ctctcaacag 420 ctaccatccc taagatgctt ggaatcttct ggatcaacctcagagggatc atctttgaag 480 cctgcctcac ccagatgttt tttatccaca acttcacacttatggagtca gcagtccttg 540 tggcaatggc ttatgacagc tatgtggcca tctgcaatccactccaatat agcgccatcc 600 tcaccaacaa ggttgtttct gtgattggtc ttggtgtgtttgtgagggct ttaattttcg 660 tcattccctc tatacttctt atattgcggt tgcccttctgtgggaatcat gtaattcccc 720 acacctactg tgagcacatg ggtcttgctc atctatcttgtgccagcatc aaaatcaata 780 ttatttatgg tttatgtgcc atttgtaatc tggtgtttgacatcacagtc attgccctct 840 cttatgtgca tattctttgt gctgttttcc gtcttcctactcatgagccc cgactcaagt 900 ccctcagcac atgtggttca catgtgtgtg taatccttgccttctataca ccagccctct 960 tttcctttat gactcattgc tttggccgaa atgtgccccgctatatccat atactcctag 1020 ccaatctcta tgttgtggtg ccaccaatgc tcaatcctgtcatatatgga gtcagaacca 1080 agcagatcta taaatgtgta aagaaaatat tattgcaggaacaaggaatg gaaaaggaag 1140 agtacctaat acatacgagg ttctgaatgc aattttatgaaatttcagtg agagaaatgt 1200 cttgtcataa aaattatatt ctaatatgtg gctttattggctctcttctg tatttaaata 1260 cattgaattt ctccatctgc ttttcatacc acattttgagatctgttgct gcattttttt 1320 ttttttt 1327 <210> SEQ ID NO 87 <211> LENGTH:1163 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7475230CB1<400> SEQUENCE: 87 gtctcttat gctatattat ggagttaaag aatggatttt ctgtttccccaagaaataga 60 caccatgctg tgagagaagt tatggtttct cactggaagc aagaaaactcatgcaagaaa 120 tgtgtctgta gggaatggca ccaatatgct tcataccaac aatacacagtttcacccttc 180 caccttcctc gtagtggggg tcccagggct ggaagatgtg catgtatggattggcttccc 240 cttctttgcg gtgtatctaa cagcccttct agggaacatc attatcctgtttgtgataca 300 gactgaacag agcctccacc aacccatgtt ttacttccta gccatgttggccggcactga 360 tctgggcttg tctacagcaa ccatccccaa gatgctggga attttctggtttaatcttgg 420 agagattgca tttggtgcct gcatcacaca gatgtatacc attcatatatgcactggcct 480 ggagtctgtg gtactgacag tcacgggcat agatcgctat attgccatctgcaaccccct 540 gagatatagc atgatcctta ccaacaaggt aatagccatt ctgggcatagtcatcattgt 600 caggactttg gtatttgtga ctccattcac atttctcacc ctgagattgcctttctgtgg 660 tgtccggatt atccctcata cctattgtga acacatgggc ttggcaaagttagcttgtgc 720 cagtattaat gttatatatg gattgattgc cttctcagtg ggatacattgacatttctgt 780 gattggattt tcctatgtcc agatcctccg agctgtcttc catctcccagcctgggatgc 840 ccggcttaag gcactcagca catgtggctc tcacgtctgt gttatgttggctttctacct 900 gccagccctc ttttccttca tgacacaccg ctttggccac aacatccctcattacatcca 960 cattcttctg gccaatctgt atgtggtttt tccccctgct cttaactctgttatctatgg 1020 ggtcaaaaca aaacagatac gagagcaggt acttaggata ctcaaccctaaaagcttttg 1080 gcattttgac cccaagagga tcttccacaa caattcagtt agacaataatgagatcataa 1140 caaaataaac actggaaaca ttt 1163 <210> SEQ ID NO 88 <211>LENGTH: 1121 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE:<221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:7475229CB1 <400> SEQUENCE: 88 ttaccaggaa tcaggataaa gtgagaagtggagcaagaat cactaatgga aagtcaataa 60 ttgtcactga tacacacaac agctttttgtgacagaaaga atgcctatag ctaacgacac 120 ccagttccat acttcttcat tcctactgctgggtatccca gggctagaag atgtgcacat 180 ctggattgga ttcccttttt tctctgtgtatcttattgca ctcctgggaa atgctgctat 240 cttctttgtg atccaaactg agcagagtctccatgagccc atgtactact gcctggccat 300 gttggattcc attgacctga gcttgtctacggccaccatt cccaaaatgc tgggcatctt 360 ctggttcaat atcaaggaaa tatcttttggaggctacctt tctcagatgt tcttcatcca 420 tttcttcact gtcatggaga gcatcgtattggtggccatg gcctttgacc gctacattgc 480 catttgcaaa cctctttggt acaccatgatcctcaccagc aaaatcatca gcctcattgc 540 aggcattgct gtcctgagga gcttgtacatggtcattcca ctggtgtttc tcctcttaag 600 gttgcccttc tgtggacatc gtatcatccctcatacttac tgtgagcaca tgggcattgc 660 ccgtctggcc tgtgccagca tcaaagtcaacattatgttt ggtcttggca gtatttctct 720 cttgttattg gatgtgctcc ttattattctctcccatatc aggatcctct atgctgtctt 780 ctgcctgccc tcctgggaag ctcgactcaaagctctcaac acctgtggct ctcacattgg 840 tgttatctta gccttttcta caccagcatttttctctttc tttacacact gctttggcca 900 tgatattccc caatatatcc acattttcttggctaatcta tatgtggttg ttcctcccac 960 cctcaatcct gtaatctatg gggtcagaaccaaacatatt agggagacag tgctgaggat 1020 tttcttcaag acagatcact aaccagttggagtttggagg gtctctctta gcattcatga 1080 tgaagcagcc actagggagg agagaagagacaccaaggaa t 1121 <210> SEQ ID NO 89 <211> LENGTH: 958 <212> TYPE: DNA<213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: misc_feature<223> OTHER INFORMATION: Incyte ID No: 7477367CB1 <400> SEQUENCE: 89taggtaactg aatattggat acatggctca cacaaatgaa tcgatggtgt ctgagtttgt 60acttttggga ctctctaatt cctggggact tcaacttttc tttttcgcca tcttctctat 120agtctatgtg acatcagtgc taggcaatgt cttaattatt gtcattattt cttttgact c 180ccatttgaac tctcctatgt acttcttgct cagtaatctt tctttcattg atatctgtca 240gtctaacttt gccaccccca agatgcttgt agactttttt attgagcgca agactatctc 300ctttgagggt tgcatggccc agatattcgt tcttcacagt tttgttggga gtgagatgat 360gttgcttgta gctatggcat atgacagatt tatagccata tgtaagcctc tgcactacag 420tacaattatg aaccggaggc tctgtgtaat ttttgtgtct atttcctggg cggtgggcgt 480tcttcattct gtgagccact tggcttttac agtggacctg ccattctgtg gtcccaatga 540ggtggatagc ttcttttgtg accttccctt ggtgatagag ctggcttgca tggatacata 600tgaaatggaa attatgaccc taacgaacag tggcctgata tcattgagct gtttcctggc 660tttaattatt tcctacacca tcattttgat cggtgtccga tgcaggtcct ccagtgggtc 720atctaaggct ctttctacat taactgccca catcacagtg gtcattcttt tcttcgggcc 780ttgcatttat ttctatatat ggccttttag cagacttcct gtggacaaat ttctttctgt 840gttctacact gtttgtactc ccttgttgaa ccccatcatc tactctttga ggaatgaaga 900tgttaaagca gccatgtgga agctgagaaa ccatcatgtg aactcctgga aaaactag 958<210> SEQ ID NO 90 <211> LENGTH: 1101 <212> TYPE: DNA <213> ORGANISM:Homo sapiens (220> FEATURE: (221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7477936CB1 SEQUENCE: 90 caaatgtgga catcaacatgaacatttctt tccaatatgc atcatttccc taccccttat 60 tctcacttat tttgatcattatgggataaa gttgacgata tggaaagagc aaaccattca 120 gtggtatcgg aatttattttgttgggactt tccaaatctc aaaatcttca gattttattc 180 ttcttgggat tctctgtggtcttcgtgggg attgtgttag gaaacctgct catcttggtg 240 actgtgacct ttgattcgctccttcacaca ccaatgtatt ttctgcttag caacctctcc 300 tgcattgata tgatcctggcttcttttgct acccctaaga tgattgtaga tttcctccga 360 gaacgtaaga ccatctcatggtggggatgt tattcccaga tgttctttat gcacctcctg 420 ggtgggagtg agatgatgttgcttgtagcc atggcaatag acaggtatgt tgccatatgc 480 aaacccctcc attacatgaccatcatgagc ccacgggtgc tcactgggct actgttatcc 540 tcctatgcag ttggatttgtgcactcatct agtcaaatgg ctttcatgtt gactttgccc 600 ttctgtggtc ccaatgttatagacagcttt ttctgtgacc ttccccttgt gattaaactt 660 gcctgcaagg acacctacatcctacagctc ctggtcattg ctgacagtgg gctcctgtca 720 ctggtctgct tcctcctcttgcttgtctcc tatggagtca taatattctc agttaggtac 780 cgtgctgcta gtcgatcctctaaggctttc tccactctct cagctcacat cacagttgtg 840 actctgttct ttgctccgtgtgtctttatc tacgtctggc ccttcagcag atactcggta 900 gataaaattc tttctgtgttttacacaatt ttcacacctc tcttaaatcc tattatttat 960 acattaagaa atcaagaggtaaaagcagcc attaaaaaaa gactctgcat ataaatttaa 1020 agcatacttt ttagatgagacttttgaaga gacactctct tgtttgtttg aacatttaag 1080 aaactcgttt ttaatgtatc a1101 <210> SEQ ID NO 91 <211> LENGTH: 1192 <212> TYPE: DNA <213>ORGANISM: Homo sapiens <220> FEATURE: (221> NAME/KEY: misc_feature <223>OTHER INFORMATION: Incyte ID No: 7475214CB1 SEQUENCE: 91 agcattttttcctcttttga tctactgtga ttttccgttg gttctgcgtt agaaataaaa 60 taaatacagtcctttttatg ttttcttttt ttcaggtaat ttaattgtct cctaagaact 120 tgacccattccatggaaaaa ataaacaacg taactgaatt cattttctgg ggtctttctc 180 agagcccagagattgagaaa gtttgttttg tggtgttttc tttcttctac ataatcattc 240 ttctgggaaatctcctcatc atgctgacag tttgcctgag caacctgttt aagtcaccca 300 tgtatttctttctcagcttc ttgtcttttg tggacatttg ttactcttca gtcacagctc 360 ccaagatgattgttgacctg ttagcaaagg acaaaaccat ctcctatgtg gggtgcatgt 420 tgcaactgcttggagtacat ttctttggtt gcactgagat cttcatcctt actgtaatgg 480 cctatgatcgttatgtggct atctgtaaac ccctacatta tatgaccatc atgaaccggg 540 agacatgcaataaaatgtta ttagggacgt gggtaggtgg gttcttacac tccattatcc 600 aagtggctctggtagtccaa ctaccctttt gtggacccaa tgagatagat cactactttt 660 gtgatgttcaccctgtgttg aaacttgcct gcacagaaac atacattgtt ggtgttgttg 720 tgacagccaacagtggtacc attgctctgg ggagttttgt tatcttgcta atctcctaca 780 gcatcatcctagtttccctg agaaagcagt cagcagaagg caggcgcaaa gccctctcca 840 cctgtggctcccacattgcc atggtcgtta tctttttcgg cccctgtact tttatgtaca 900 tgcgccctgatacgaccttt tcagaggata agatggtggc tgtattttac accattatca 960 ctcccatgttaaatcctctg atttatacac tgagaaatgc agaagtaaag aatgcaatga 1020 agaaactgtggggcagaaat gttttcttgg aggctaaagg gaaatagttg gacttaataa 1080 tttaagctagatgaccttaa aatttctcag ccttggttaa ctcatctgtg caatcaagac 1140 aataacaacctcatgggatt tggagtggaa aaatgagaca ataacacatt ca 1192 <210> SEQ ID NO 92<211> LENGTH: 1341 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220>FEATURE: <221> NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte IDNo: 55036157CB1 <400> SEQUENCE: 92 tttgcaagta ttagcttaaa aatactgacttgaagatcat tgaaatattc aaaatacaaa 60 atagacactc aaagttttta attattataaacataggtaa aatattatca tatagaatac 120 cagttactag aaaataaaga ttactacatgctaaattggg ataaattatg attcagttaa 180 ttgaaccgga gttaaatgat catatataaacaagggatca ctttcctaca aaaggagaat 240 aacaatacaa ttcacctaaa taccatgttttttctctccc ctgcagaaac tcatcaaaga 300 atggcagcag aaaaccattc ttttgtgactaagtttattc tggttgggct aacagagaag 360 tcagagctac agctgcccct cttcctcgtcttcctgggaa tctatgtagt cacagtgctg 420 gggaacctgg gcatgatcac actgattgggctcagttctc acctgcacac acctatgtac 480 tgtttcctca gcagtctgtc cttcattgacttctgccatt ccactgtcat tacccctaag 540 atgctggtga actttgtgac agagaagaacatcatctcct accctgaatg catgactcag 600 ctctacttct tcctcgtttt tgctattgcagagtgtcaca tgttggctgc aatggcatat 660 gacggctacg tggccatctg tagccccttgctgtacagca tcatcatatc caataaggct 720 tgcttttctc tgattttagt ggtgtatgtaataggcctga tttgtgcgtc agctcatata 780 ggctgtatgt ttagggttca attctgcaaatttgatgtga tcaaccatta tttctgtgat 840 cttatttcta tcttgaagct ctcctgttctagtacttaca ttaatgagtt actgatttta 900 atctttagtg gaattaacat ccttgtccccagcctgacca tcctcagctc ttacatcttc 960 atcattgcca gcatcctccg cattcgctacactgagggca ggtccaaagc cttcagcact 1020 tgcagctccc acatctcggc tgtttctgttttctttgggt ctgcagcatt catgtacctg 1080 cagccatcat ctgtcagctc catggaccaggggaaagtgt cctctgtgtt ttatactatt 1140 gttgtgccca tgctgaaccc cctgatctacagcctgagga ataaagatgt ccacgttgcc 1200 ctgaagaaaa cgctagggaa aagaacattcttatgaacag aagtacaatg aaaaagattg 1260 cattagatct aagtttttgg ctatgatattgtatgaaatg atgtctttca ctttagtgca 1320 tctgtcaaca ttctttctaa t 1341 <210>SEQ ID NO 93 <211> LENGTH: 1114 <212> TYPE: DNA <213> ORGANISM: Homosapiens <220> FEATURE: <221> NAME/KEY: misc_feature <223> OTHERINFORMATION: Incyte ID No: 7475226CB1 <400> SEQUENCE: 93 taatgtagcaggaatgcaga aatcatgact ttggtttctt ttttctcttt cctctccaag 60 ccattgataatgctccttag caattcaagc tggaggctat cccagccttc ttttctcctg 120 gtagggattccaggtttaga ggaaagccag cactggattg cactgcccct gggcatcctt 180 tacctccttgctttagtggg caatgttacc attctcttca tcatctggat ggacccatcc 240 ttgcaccaatctatgtacct cttcctgtcc atgctagctg ccatcgacct ggttctggcc 300 tcctccactgcacccaaagc ccttgcagtg ctcctggttc atgcccacga gattgggtac 360 atcgtctgcctgatccagat gttcttcatc catgcattct cctccatgga gtcaggggta 420 cttgtggccatggctctgga tcgctatgta gccatttgtc accccttgca ccattccaca 480 atcctgcatccaggggtcat agggcgcatc ggaatggtgg tgctggtgag gggattacta 540 ctccttatccccttccccat tttgttggga acacttatct tctgccaagc caccatcata 600 ggccatgcctattgtgaaca tatggctgtt gtgaaacttg cctgctcaga aaccacagtc 660 aatcgagcttatgggctgac tatggccttg cttgtgattg ggctggatgt tctggccatt 720 ggtgtttcctatgcccacat cctccaggca gtgctgaagg taccagggag tgaggcccga 780 cttaaggcgtttagcacatg tggctctcat atttgtgtca tcctggtctt ctatgtccct 840 ggaattttctccttcctcac tcaccgcttt ggtcatcatg taccccatca tgtccatgtt 900 cttctggccacacggtatct cctcatgcca cctgcgctca atcctcttgt ctatggagtg 960 aagactcagcagatccgcca gcgagtgctc agagtgttta cacaaaagga ttgatctgaa 1020 catattctcattgtttcctt cggaggcttc ttctgcggac cacagccagg agcctgtgac 1080 tggtgtagattacatgaata cagaccactc tgca 1114 <210> SEQ ID NO 94 <211> LENGTH: 960<212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No: 7477353CB1<400> SEQUENCE: 94 gaaggatcgt atgaatgccc catggaaaat tacaatcaaacgtcaactga tttcatctta 60 ttggggctgt tcccaccatc aaaaattggc cttttcctcttcattctctt tgttctcatt 120 ttcctaatgg ctctaattgg aaacctatcc atgattcttctcatcttctt ggacacccat 180 ctccacacac ccatgtattt cctgcttagt cagctctccctcattgacct aaattacatc 240 tctacgattg ttcctaagat ggcttctgat tttctgtatggaaacaagtc tatctccttc 300 attgggtgtg ggattcagag tttcttcttc atgacttttgcaggtgcaga agcgctgctc 360 ctgacatcaa tggcctatga tcgttatgtg gccatttgctttcctctcca ctatcccatc 420 cgtatgagca aaagaatgta tgtgctgatg ataacaggatcttggatgat aggctccatc 480 aactcttgtg ctcacacagt atatgcattc cgtatcccatattgcaagtc cagagccatc 540 aatcattttt tctgtgatgt tccagctatg ttgacattagcctgtacaga cacctgggtc 600 tatgagtaca cagtgttttt gagcagcacc atctttcttgtgtttccctt cactggcatt 660 gcgtgttcct atggctgggt tctccttgct gtctaccgcatgcactctgc agaagggagg 720 aaaaaggcct attcgacctg cagcacccac ctcactgtagtaactttcta ctatgcaccc 780 tttgcttata cctatctatg tccaagatcc ctgcgatctctgacagagga caaggttctg 840 gctgttttct acaccatcct caccccaatg ctcaaccccatcatctacag cctgagaaac 900 aaggaggtga tgggggccct gacacgagtg attcagaatatcttctcggt gaaaatgtag 960 <210> SEQ ID NO 95 <211> LENGTH: 1269 <212>TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY:misc_feature <223> OTHER INFORMATION: Incyte ID No: 55036208CB1 <400>SEQUENCE: 95 ctccataatt ttataagtga tgctgtattg aaagaacata tttcgttcagattctatact 60 tcttgacctt ttagtttcct acttctattc atgctgtatt gatcacccaactacagaatt 120 taccaaaatc acacgattta taagacactg ggtaaatgtt taccaaattaataagatggt 180 tttgtggtac taggtaaaaa gcacattcat catggcatgg gagaatcagaccttcaactc 240 cgacttcatc ctccttggaa tcttcaatca cagcccacca cacacgttcctcttctttct 300 ggtcctgggc atctttttag tggccttcat gggaaactct gtcatggttctcctcatcta 360 cctggacacc cagctccaca cccccatgta cttcctcctc agccaactgtccctcatgga 420 cctcatgctc atctgcacca ccgtacccaa gatggccttc aactacttgtctggcagcaa 480 gtccatttct atggctggtt gtgtcacaca aattttcttc tatatatcactgtctggctc 540 tgaatgtttt cttttggctg ttatggctta tgaccgctat attgctatttgccaccctct 600 aagatatacc aatctcatga atcctaaaat ttgtggactt atggctaccttctcctggat 660 cctgggctct acagatggaa tcattgatgc tgtagccaca ttttccttctccttttgtgg 720 gtctcgggaa atagcccact tcttctgtga attcccttcc ctactaatcctctcatgcaa 780 tgacacatca atatttgaag aggttatttt catctgctgt atagtaatgcttgttttccc 840 tgttgcaatc atcattgctt cctatgctgg agttattctg gctgtcattcacatgggatc 900 tggagagggt cgtcgcaaaa ctttcacgac ctgttcctct cacctcatggtggtgggaat 960 gtactatgga gcagctttgt tcatgtacat acggcccaca tctgatcactccccaacgca 1020 ggacaagatg gtgtctgtat tctacaccat cctcactccc atgctgaatcccctcatcta 1080 cagcctccgc aacaaggagg tgactagagc attcatgaag atcttaggaaagggcaagtc 1140 tgagagtgag ttacctcata aactttatgt tttgctgttt gctaaattcttctttctaat 1200 atccatcttt ttctatgatg tcaaaatact agcattgatt atgtacattgcctaacatat 1260 ttatgggca 1269 <210> SEQ ID NO 96 <211> LENGTH: 2197<212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221>NAME/KEY: misc_feature <223> OTHER INFORMATION: Incyte ID No:55019501CB1 <400> SEQUENCE: 96 tcatccccac tcccactgta acagatgcaggaattgaagt ttagcaagac tggcttggtg 60 aaggtcagag taggaggggg tgtgagatgcgcatactgct gtcttgacgc cccatccagg 120 gggctaaaga gggtcaggca ggaggaagcctgagagaaag cagacaccgt gagaaaatga 180 ctcatttcat cccgtgccag tcactcacccaaactctctt cactcatcat cgcagctccc 240 agaagatgcc ttagcatgag aggtgacaaccacagctgct tctgggacac cccaaaggac 300 tttatcctcc tgggcatttc cgacaggccatggctggagc tcccagtctt tgcagtcctc 360 ctggtgttct acattctggc tatgctggggaacatctcta tcatcctggt atcccagctg 420 gatcctcagc tccacagccc catgtacatattcctcagcc acttgtcctt cctggatctc 480 tgctacacca ccaccactgt ccctcagatgctgttcaaca tggggagctc ccagaagacc 540 atcagttacg gtggctgcac ggtgcaatacgccattttcc actggctggg ctgcaccgag 600 tgcgttgtct tggcggccat ggctctggaccgctacgtgg ccatctgtga gccactccgc 660 tatgctatca tcatgcaccg cccactctgccagcagctcg tggctatggc ctggctcagc 720 ggcttcggca actcccttgt tcaggtcatcctgacagtgc aattgccttt ctgtggccgg 780 caggtgctga acaacttctt ctgcgaggtgccagccatga tcaagctgtc ctgtgctgat 840 actacggcga atgatgccac cctggctgtgctggtggcct tctttgtgct ggtccctctg 900 gccctcatcc tcctctccta cggcttcattgctcgggcag tgatgaggat ccagtcctcc 960 aggggacggc acaaggcctt cgggacttgctcttcccacc tgttggtggt ctccctcttc 1020 tacctgcccg ccatttacat gtacctgcagccgccatcca gttactcaca ggagcagggc 1080 aagttcatct ccctcttcta ttctataatcacccccaccc ttaacccttt catctacacc 1140 ttgaggaata aggacgtgaa gggagctctccgaagactcc tggcaaggac cggaaggctg 1200 tgtggaaggt gaaaaatgta atcccggaagacctacacct ctggcagaac tccgcagcaa 1260 ggactctggg gggtgggtag ggttgtagctcaggggtggt acagcacttc cttggcatgt 1320 gggaaggact gagttcaacc cctagggctgtaggaaattc ttggaacagt aggttctttg 1380 agagatttga aagaaaacaa aaaacatccaaaagcatttc accttccgtg tggtgatgag 1440 gctcaaagtc ccgcatctga gcgttaagttccattctcag agcacagttc taagaagcca 1500 tatatcttca agaagcgctt aaatgacttgatgctcacaa gtactcgtta cgctgtttaa 1560 cttctaattc cctggctctt cctgttttcttcctcttcct gtatttcctc tctcgtttcc 1620 catgtatctt tttaaacccc tttcttccattacagtcact ccagatgtgt acaaaatgaa 1680 cttgacacag agtcttacct cgtttataataaacgtctgt tcttcgtgga tcaaaatcaa 1740 tacattttgt atttattttc caaaatgtcataagaatgac atgactgcat ccttctattc 1800 ataaccataa acaattttct tttccctctggtttaaactg tccttacaga aagttttccc 1860 accgttgagt gggaactttc tgctagaaggctagatgact ccctgttagg gtacaggggt 1920 acaaacaagt acatctcccc tctcagcttctagatggacg tattccagtg gagaatgcag 1980 taacaaatac aatacagtta aaatgataaaacctaacata agagctgaag atgtttaact 2040 cagtctagag ctcctgccta gcttggtcctggcttcactg cccagaacca cacacaagaa 2100 atgttgacag tgattcattc aagctaacatttgtggaagg tttctgtgat gctggtgata 2160 cactgagtgt ttgtaagtaa cgatctgtgttatactg 2197

What is claimed is:
 1. An isolated polypeptide selected from the groupconsisting of: a) a polypeptide comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:1-48, b) a polypeptidecomprising a naturally occurring amino acid sequence at least 90%identical to an amino acid sequence selected from the group consistingof SEQ ID NO:1-36 and SEQ ID NO:38-48, c) a naturally occurringpolypeptide comprising an amino acid sequence at least 91% identical toan amino acid sequence selected from the group consisting of SEQ IDNO:37, d) a biologically active fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-48, and e) an immunogenic fragment of a polypeptide having an aminoacid sequence selected from the group consisting of SEQ ID NO:1-48. 2.An isolated polypeptide of claim 1 comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:1-48.
 3. An isolatedpolynucleotide encoding a polypeptide of claim
 1. 4. An isolatedpolynucleotide encoding a polypeptide of claim
 2. 5. An isolatedpolynucleotide of claim 4 comprising a polynucleotide sequence selectedfrom the group consisting of SEQ ID NO:49-96.
 6. A recombinantpolynucleotide comprising a promoter sequence operably linked to apolynucleotide of claim
 3. 7. A cell transformed with a recombinantpolynucleotide of claim
 6. 8. A transgenic organism comprising arecombinant polynucleotide of claim
 6. 9. A method of producing apolypeptide of claim 1, the method comprising: a) culturing a cell underconditions suitable for expression of the polypeptide, wherein said cellis transformed with a recombinant polynucleotide, and said recombinantpolynucleotide comprises a promoter sequence operably linked to apolynucleotide encoding the polypeptide of claim 1, and b) recoveringthe polypeptide so expressed.
 10. A method of claim 9, wherein thepolypeptide comprises an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48.
 11. An isolated antibody whichspecifically binds to a polypeptide of claim
 1. 12. An isolatedpolynucleotide selected from the group consisting of: a) apolynucleotide comprising a polynucleotide sequence selected from thegroup consisting of SEQ ID NO:49-96, b) a polynucleotide comprising anaturally occurring polynucleotide sequence at least 90% identical to apolynucleotide sequence selected from the group consisting of SEQ IDNO:49-84 and SEQ ID NO:86-96, c) a naturally occurring polynucleotidecomprising a polynucleotide sequence at least 91% identical to thepolynucleotide sequence of SEQ ID NO:85, d) a polynucleotidecomplementary to a polynucleotide of a), e) a polynucleotidecomplementary to a polynucleotide of b), and f) an RNA equivalent ofa)-e).
 13. An isolated polynucleotide comprising at least 60 contiguousnucleotides of a polynucleotide of claim
 12. 14. A method of detecting atarget polynucleotide in a sample, said target polynucleotide having asequence of a polynucleotide of claim 12, the method comprising: a)hybridizing the sample with a probe comprising at least 20 contiguousnucleotides comprising a sequence complementary to said targetpolynucleotide in the sample, and which probe specifically hybridizes tosaid target polynucleotide, under conditions whereby a hybridizationcomplex is formed between said probe and said target polynucleotide orfragments thereof, and b) detecting the presence or absence of saidhybridization complex, and, optionally, if present, the amount thereof.15. A method of claim 14, wherein the probe comprises at least 60contiguous nucleotides.
 16. A method of detecting a targetpolynucleotide in a sample, said target polynucleotide having a sequenceof a polynucleotide of claim 12, the method comprising: a) amplifyingsaid target polynucleotide or fragment thereof using polymerase chainreaction amplification, and b) detecting the presence or absence of saidamplified target polynucleotide or fragment thereof, and, optionally, ifpresent, the amount thereof.
 17. A composition comprising a polypeptideof claim 1 and a pharmaceutically acceptable excipient.
 18. Acomposition of claim 17, wherein the polypeptide comprises an amino acidsequence selected from the group consisting of SEQ ID NO:1-48.
 19. Amethod for treating a disease or condition associated with decreasedexpression of functional GCREC, comprising administering to a patient inneed of such treatment the composition of claim
 17. 20. A method ofscreening a compound for effectiveness as an agonist of a polypeptide ofclaim 1, the method comprising: a) exposing a sample comprising apolypeptide of claim 1 to a compound, and b) detecting agonist activityin the sample.
 21. A composition comprising an agonist compoundidentified by a method of claim 20 and a pharmaceutically acceptableexcipient.
 22. A method for treating a disease or condition associatedwith decreased expression of functional GCREC, comprising administeringto a patient in need of such treatment a composition of claim
 21. 23. Amethod of screening a compound for effectiveness as an antagonist of apolypeptide of claim 1, the method comprising: a) exposing a samplecomprising a polypeptide of claim 1 to a compound, and b) detectingantagonist activity in the sample.
 24. A composition comprising anantagonist compound identified by a method of claim 23 and apharmaceutically acceptable excipient.
 25. A method for treating adisease or condition associated with overexpression of functional GCREC,comprising administering to a patient in need of such treatment acomposition of claim
 24. 26. A method of screening for a compound thatspecifically binds to the polypeptide of claim 1, the method comprising:a) combining the polypeptide of claim 1 with at least one test compoundunder suitable conditions, and b) detecting binding of the polypeptideof claim 1 to the test compound, thereby identifying a compound thatspecifically binds to the polypeptide of claim
 1. 27. A method ofscreening for a compound that modulates the activity of the polypeptideof claim 1, the method comprising: a) combining the polypeptide of claim1 with at least one test compound under conditions permissive for theactivity of the polypeptide of claim 1, b) assessing the activity of thepolypeptide of claim 1 in the presence of the test compound, and c)comparing the activity of the polypeptide of claim 1 in the presence ofthe test compound with the activity of the polypeptide of claim 1 in theabsence of the test compound, wherein a change in the activity of thepolypeptide of claim 1 in the presence of the test compound isindicative of a compound that modulates the activity of the polypeptideof claim
 1. 28. A method of screening a compound for effectiveness inaltering expression of a target polynucleotide, wherein said targetpolynucleotide comprises a sequence of claim 5, the method comprising:a) exposing a sample comprising the target polynucleotide to a compound,under conditions suitable for the expression of the targetpolynucleotide, b) detecting altered expression of the targetpolynucleotide, and c) comparing the expression of the targetpolynucleotide in the presence of varying amounts of the compound and inthe absence of the compound.
 29. A method of assessing toxicity of atest compound, the method comprising: a) treating a biological samplecontaining nucleic acids with the test compound, b) hybridizing thenucleic acids of the treated biological sample with a probe comprisingat least 20 contiguous nucleotides of a polynucleotide of claim 12 underconditions whereby a specific hybridization complex is formed betweensaid probe and a target polynucleotide in the biological sample, saidtarget polynucleotide comprising a polynucleotide sequence of apolynucleotide of claim 12 or fragment thereof, c) quantifying theamount of hybridization complex, and d) comparing the amount ofhybridization complex in the treated biological sample with the amountof hybridization complex in an untreated biological sample, wherein adifference in the amount of hybridization complex in the treatedbiological sample is indicative of toxicity of the test compound.
 30. Adiagnostic test for a condition or disease associated with theexpression of GCREC in a biological sample, the method comprising: a)combining the biological sample with an antibody of claim 11, underconditions suitable for the antibody to bind the polypeptide and form anantibody:polypeptide complex, and b) detecting the complex, wherein thepresence of the complex correlates with the presence of the polypeptidein the biological sample.
 31. The antibody of claim 11, wherein theantibody is: a) a chimeric antibody, b) a single chain antibody, c) aFab fragment, d) a F(ab′)₂ fragment, or e) a humanized antibody.
 32. Acomposition comprising an antibody of claim 11 and an acceptableexcipient.
 33. A method of diagnosing a condition or disease associatedwith the expression of GCREC in a subject, comprising administering tosaid subject an effective amount of the composition of claim
 32. 34. Acomposition of claim 32, wherein the antibody is labeled.
 35. A methodof diagnosing a condition or disease associated with the expression ofGCREC in a subject, comprising administering to said subject aneffective amount of the composition of claim
 34. 36. A method ofpreparing a polyclonal antibody with the specificity of the antibody ofclaim 11, the method comprising: a) immunizing an animal with apolypeptide consisting of an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48, or an immunogenic fragment thereof, underconditions to elicit an antibody response, b) isolating antibodies fromsaid animal, and c) screening the isolated antibodies with thepolypeptide, thereby identifying a polyclonal antibody which bindsspecifically to a polypeptide comprising an amino acid sequence selectedfrom the group consisting of SEQ ID NO:1-48.
 37. A polyclonal antibodyproduced by a method of claim
 36. 38. A composition comprising thepolyclonal antibody of claim 37 and a suitable carrier.
 39. A method ofmaking a monoclonal antibody with the specificity of the antibody ofclaim 11, the method comprising: a) immunizing an animal with apolypeptide consisting of an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48, or an immunogenic fragment thereof, underconditions to elicit an antibody response, b) isolating antibodyproducing cells from the animal, c) fusing the antibody producing cellswith immortalized cells to form monoclonal antibody-producing hybridomacells, d) culturing the hybridoma cells, and e) isolating from theculture monoclonal antibody which binds specifically to a polypeptidecomprising an amino acid sequence selected from the group consisting ofSEQ ID NO:1-48.
 40. A monoclonal antibody produced by a method of claim39.
 41. A composition comprising the monoclonal antibody of claim 40 anda suitable carrier.
 42. The antibody of claim 11, wherein the antibodyis produced by screening a Fab expression library.
 43. The antibody ofclaim 11, wherein the antibody is produced by screening a recombinantimmunoglobulin library.
 44. A method of detecting a polypeptidecomprising an amino acid sequence selected from the group consisting ofSEQ ID NO:1-48 in a sample, the method comprising: a) incubating theantibody of claim 11 with a sample under conditions to allow specificbinding of the antibody and the polypeptide, and b) detecting specificbinding, wherein specific binding indicates the presence of apolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48 in the sample.
 45. A method of purifying apolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48 from a sample, the method comprising: a)incubating the antibody of claim 11 with a sample under conditions toallow specific binding of the antibody and the polypeptide, and b)separating the antibody from the sample and obtaining the purifiedpolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48.
 46. A microarray wherein at least oneelement of the microarray is a polynucleotide of claim
 13. 47. A methodof generating an expression profile of a sample which containspolynucleotides, the method comprising: a) labeling the polynucleotidesof the sample, b) contacting the elements of the microarray of claim 46with the labeled polynucleotides of the sample under conditions suitablefor the formation of a hybridization complex, and c) quantifying theexpression of the polynucleotides in the sample.
 48. An array comprisingdifferent nucleotide molecules affixed in distinct physical locations ona solid substrate, wherein at least one of said nucleotide moleculescomprises a first oligonucleotide or polynucleotide sequencespecifically hybridizable with at least 30 contiguous nucleotides of atarget polynucleotide, and wherein said target polynucleotide is apolynucleotide of claim
 12. 49. An array of claim 48, wherein said firstoligonucleotide or polynucleotide sequence is completely complementaryto at least 30 contiguous nucleotides of said target polynucleotide. 50.An array of claim 48, wherein said first oligonucleotide orpolynucleotide sequence is completely complementary to at least 60contiguous nucleotides of said target polynucleotide.
 51. An array ofclaim 48, wherein said first oligonucleotide or polynucleotide sequenceis completely complementary to said target polynucleotide.
 52. An arrayof claim 48, which is a microarray.
 53. An array of claim 48, furthercomprising said target polynucleotide hybridized to a nucleotidemolecule comprising said first oligonucleotide or polynucleotidesequence.
 54. An array of claim 48, wherein a linker joins at least oneof said nucleotide molecules to said solid substrate.
 55. An array ofclaim 48, wherein each distinct physical location on the substratecontains multiple nucleotide molecules, and the multiple nucleotidemolecules at any single distinct physical location have the samesequence, and each distinct physical location on the substrate containsnucleotide molecules having a sequence which differs from the sequenceof nucleotide molecules at another distinct physical location on thesubstrate.
 56. A method of identifying a compound that modulates, mimicsand/or blocks an olfactory and/or taste sensation, the methodcomprising: a) contacting the compound with an olfactory and/or tastereceptor polypeptide selected from the group consisting of: i) apolypeptide having an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48, ii) a biologically active fragment of apolypeptide having an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-48, and iii) an olfactory and/or tastereceptor having an amino acid sequence at least 90% identical to anamino acid sequence selected from the group consisting of SEQ IDNO:1-48. b) identifying whether the compound specifically binds toand/or affects the activity of said receptor polypeptide.
 57. The methodof claim 56, wherein said receptor polypeptide is expressed on thesurface of a mammalian cell.
 58. The method of claim 57, wherein saidmammalian cell expresses a G-protein.
 59. The method of claim 58,wherein said mammalian cell expresses a plurality of G-protein coupledreceptors.
 60. The method of claim 59, wherein said mammalian cellexpresses another olfactory and/or taste receptor polypeptide.
 61. Themethod of claim 56, wherein said receptor polypeptide is fused toanother polypeptide.
 62. A polypeptide of claim 1, comprising the aminoacid sequence of SEQ ID NO:1.
 63. A polypeptide of claim 1, comprisingthe amino acid sequence of SEQ ID NO:2.
 64. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:3.
 65. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:4.
 66. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:5.
 67. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:6.
 68. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:7.
 69. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:8.
 70. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:9.
 71. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:10.
 72. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:11.
 73. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:12.
 74. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:13.
 75. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:14.
 76. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:15.
 77. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:16.
 78. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:17.
 79. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:18.
 80. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:19.
 81. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:20.
 82. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:21.
 83. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:22.
 84. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:23.
 85. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:24.
 86. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:25.
 87. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:26.
 88. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:27.
 89. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:28.
 90. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:29.
 91. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:30.
 92. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:31.
 93. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:32.
 94. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:33.
 95. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:34.
 96. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:35.
 97. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:36.
 98. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:37.
 99. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:38.
 100. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:39.
 101. A polypeptideof claim 1, comprising the amino acid sequence of SEQ ID NO:40.
 102. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:41.
 103. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:42.
 104. A polypeptide of claim 1, comprising the aminoacid sequence of SEQ ID NO:43.
 105. A polypeptide of claim 1, comprisingthe amino acid sequence of SEQ ID NO:44.
 106. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:45.
 107. A polypeptideof claim 1, comprising the amino acid sequence of SEQ ID NO:46.
 108. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:47.
 109. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:48.
 110. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:49.
 111. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:50.
 112. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:51.
 113. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:52.
 114. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:53.
 115. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:54.
 116. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:55.
 117. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:56.
 118. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:57.
 119. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:58.
 120. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:59.
 121. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:60.
 122. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:61.
 123. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:62.
 124. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:63.
 125. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:64.
 126. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:65.
 127. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:66.
 128. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:67.
 129. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:68.
 130. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:69.
 131. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:70.
 132. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:71.
 133. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:72.
 134. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:73.
 135. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:74.
 136. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:75.
 137. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:76.
 138. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:77.
 139. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:78.
 140. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:79.
 141. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:80.
 142. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:81.
 143. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:82.
 144. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:83.
 145. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:84.
 146. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:85.
 147. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:86.
 148. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:87.
 149. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:88.
 150. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:89.
 151. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:90.
 152. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:91.
 153. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:92.
 154. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:93.
 155. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:94.
 156. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:95.
 157. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:96.